Virology & Mycology Infectious Diseases
 
   Publications A-Z
A
»Accounting & Marketing
» Addiction Research & Therapy
» Advanced Chemical Engineering
»Advances in Automobile Engineering
»Advances in Crop Science and Technology
»Advances in Dairy Research
»Advancements in Genetic Engineering
»Advances in Pharmacoepidemiology & Drug Safety
»Advances in Robotics & Automation
»Advanced Techniques in Biology & Medicine
»Advance Research in Meteorological Sciences
»Aeronautics & Aerospace Engineering
»Aging Science
»Agrotechnology
»AIDS & Clinical Research
»Alcoholism and Drug Dependence
»Allergy & Therapy
»Alternative & Integrative Medicine
»Air & Water borne Diseases
»Alzheimers Disease & Parkinsonism
»Analytical & Bioanalytical Techniques
»Anaplastology
»Anatomy & Physiology
»Ancient Diseases & Preventive Remedies
»Andrology-Open Access
»Anesthesia & Clinical Research
»Angiology: Open Access
»Antivirals & Antiretrovirals
»Anthropology
»Applied & Computational Mathematics
»Applied Mechanical Engineering
»Aquaculture Research & Development
» Arabian Journal Business and Management Review
»Architectural Engineering Technology
»Arthritis
»Arts and Social Sciences Journal
» Astrobiology & Outreach
»Astrophysics & Aerospace technology
»Autacoids
»Automatic Control of Physiological State and Function
»Autism-Open Access
  
B
»Bacteriology & Parasitology
»Bioanalysis & Biomedicine
»Bioceramics Development and Applications
»Biochemistry and Analytical Biochemistry
»Biochemistry & Pharmacology: Open Access
»Biochips & Tissue Chips
»Biodiversity & Endangered Species
»Bioenergetics: Open Access
»Bioengineering & Biomedical Science
»Bioequivalence & Bioavailability
»Biosafety & Health Education
»Biofertilizers & Biopesticides
»Biometrics & Biostatistics
»Biomimetics Biomaterials and Tissue Engineering
»Biomolecular Research & Therapeutics
» Biomusical Engineering
»Biochemistry & Physiology: Open Access
»Biological Systems- Open Access
»Biology and Medicine
»Bioprocessing & Biotechniques
»Bioremediation & Biodegradation
»Biosafety
»Biosensors & Bioelectronics
» Biosensors Journal
»Biotechnology & Biomaterials
»Bioterrorism & Biodefense
»Blood Disorders & Transfusion
»Blood & Lymph
»Bone Marrow Research
»Brain Disorders & Therapy
»Business and Economics Journal
»Business and Financial Affairs
  
C
»Cancer Science & Therapy
»Climatology & Weather forecasting
»Carcinogenesis & Mutagenesis
»Cardiovascular Diseases & Diagnosis
»Cardiovascular Pharmacology: Open Access
»Cell & Developmental Biology
»Cell Science & Therapy
»Chemical Engineering & Process Technology
»Chemical Sciences Journal
»Chemotherapy: Open Access
»Child and Adolescent Behavior
»Chromatography & Separation Techniques
»Civil & Environmental Engineering
»Civil & Legal Sciences
»Clinical & Cellular Immunology
»Clinical Case Reports
»Clinical & Experimental Cardiology
»Clinical & Experimental Dermatology Research
»Clinical & Experimental Ophthalmology
»Clinical & Experimental Pathology
»Clinical & Experimental Pharmacology
»Clinical Microbiology: Open Access
»Clinical Pharmacology & Biopharmaceutics
»Clinical Research & Bioethics
»Clinical Research on Foot & Ankle
»Clinical Toxicology
»Clinical Trials
»Clinics in Mother and Child Health
»Cloning & Transgenesis
»Community Medicine & Health Education
»Communication Disorders, Deaf Studies & Hearing Aids
»Computer Science & Systems Biology
» Current Synthetic & Systems Biology
»Cytology & Histology
D
»Data Mining in Genomics & Proteomics
»Defense Management
»Dentistry
»Depression and Anxiety
»Developing Drugs
»Diabetes & Metabolism
»Drug Designing
»Drug Metabolism & Toxicology
  
E
»Earth Science & Climatic Change
»Ecosystem & Ecography
»Endocrinology & Metabolic Syndrome
»Entomology, Ornithology & Herpetology
»Environmental & Analytical Toxicology
»Epidemiology: Open Access
»Emergency Medicine
»Ergonomics
»Electrical & Electronics
»Enzyme Engineering
»Entrepreneurship & Organization Management
  
F
»Family Medicine & Medical Science Research
»Fermentation Technology
»Fertilization: In Vitro - IVF-Worldwide
»Fisheries and Aquaculture Journal
»Fisheries & Livestock Production
»Food Processing & Technology
»Forensic Biomechanics
»Forensic Research
»Forest Research: Open Access
»Fundamentals of Renewable Energy and Applications
»Fungal Genomics & Biology
  
G
»Gastrointestinal & Digestive System
»Genetic Syndromes & Gene Therapy
»Gene Technology
»Generalized Lie Theory and Applications
»Glycobiology
»Glycomics & Lipidomics
»Gynecology& Obstetrics
»General Medicine
»General Practice
»Geography & Natural Disasters
»Geology & Geosciences
»Geophysics & Remote Sensing
»Gerontology & Geriatric Research
»Global Economics
»Global Journal of Technology and Optimization
  
H
»Hair : Therapy & Transplantation
»Hematology & Thromboembolic Diseases
»Health Care : Current Reviews
»Health & Medical Informatics
»Hereditary Genetics
»Homeopathy & Ayurvedic Medicine
»Horticulture
»Hotel & Business Management
»Human Genetics & Embryology
»Hydrology: Current Research
»Hypertension- Open Access
  
I
»Industrial Engineering & Management
»Irrigation and Drainage Systems Engineering
»Infectious Diseases and Therapy
»Information Technology & Software Engineering
»Intellectual Property Rights: Open Access
»Integrative Oncology
»Internal Medicine
»International Journal of Accounting Research
»International Journal of Advanced Innovations, Thoughts & Ideas
»International Journal of Biomedical Data Mining
»International Journal of Economics and Management Science
»International Journal of Sensor Networks and Data Communications
»International Journal of Swarm Intelligence and Evolutionary Computation
»International Journal of waste resources
»International Journal of Genomic Medicine
»International Journal of Physical Medicine & Rehabilitation
»Innovative Energy Policies
»Immunome Research
  
J
»JBR Journal of Interdisciplinary Medicine and Dental Science
»JBR Journal of Clinical Diagnosis and Research
»JBR Journal of Young Scientist
  
L
»Liver
» Leukemia
» Lovotics
  
M
»Marine Science: Research & Development
»Malaria Chemotherapy, Control & Elimination
»Mass Communication & Journalism
»Material Sciences & Engineering
»Medicinal Chemistry
»Medicinal & Aromatic Plants
»Medical Diagnostic Methods
»Medical Microbiology & Diagnosis
»Medical & Surgical Urology
»Membrane Science & Technology
»Metabolic Syndrome
»Metabolomics:Open Access
»Microbial & Biochemical Technology
»Modern Chemistry & Applications
»Molecular Biology
»Molecular Biomarkers & Diagnosis
»Molecular and Genetic Medicine
»Molecular Imaging & Dynamics
»Molecular Pharmaceutics & Organic Process Research
»Mycobacterial Diseases
N
»Natural Products Chemistry & Research
»Nanomedicine & Biotherapeutic Discovery
»Nanomedicine & Nanotechnology
»Neonatal Biology
»Nephrology & Therapeutics
»Neurology & Neurophysiology
»Neuroinfectious Diseases
»Neurological Disorders
»Novel Physiotherapies
»Nuclear Medicine & Radiation Therapy
»Nutrition & Food Sciences
»Nutritional Disorders & Therapy
»Nursing & Care
  
O
»Obesity & Weight Loss Therapy
»Oceanography-Open Access
»Occupational Medicine & Health Affairs
»OMICS Journal of Radiology
»Osteoporosis and Physical Activity
»Oral Health and Dental Management
»Oral Hygiene & Health
»Organic Chemistry: Current Research
»Orthopedic & Muscular System: Current Research
»Otolaryngology
  
P
»Pain & Relief
»Palliative Care & Medicine
»Pancreatic Disorders & Therapy
»Pediatrics & Therapeutics
»Petroleum & Environmental Biotechnology
»Pharmaceutica Analytica Acta
»Pharmaceutical Regulatory Affairs: Open Access
»Pharmacogenomics & Pharmacoproteomics
»Pharmacovigilance
»Physical Chemistry & Biophysics
»Physical Mathematics
»Plant Pathology & Microbiology
»Plant Biochemistry & Physiology
»Pollution Effects & Control
»political Sciences & public affairs
»Poultry, Fisheries & Wildlife Sciences
»Powder Metallurgy & Mining
»Primatology
»Primary Health Care: Open Access
»Probiotics & Health
» Phylogenetics & Evolutionary Biology
»Proteomics & Bioinformatics
»Phylogenetics & Evolutionary Biology
»Psychology & Psychotherapy
»Psychological Abnormalities in Children
»Pulmonary & Respiratory Medicine
  
R
»Reproductive System & Sexual Disorders
»Research and Development
»Review of Public Adminstration and Management
»Rheumatology: Current Research
»Rice Research: Open Access
  
S
» Single Cell Biology
»Sleep Disorders & Therapy
»Socialomics
»Sociology and Criminology-Open Access
»Sports Medicine & Doping Studies
»Spine
»Stem Cell Research & Therapy
»Steroids & Hormonal Science
»Stock & Forex Trading
»Surgery: Current Research
  
T
»Telecommunications System & Management
»Textile Science & Engineering
»Theoretical and Computational Chemistry:Open Access
»Thermodynamics & Catalysis
»Thyroid Disorders & Therapy
»Tissue Science & Engineering
»Translational Medicine
»Transplantation Technologies & Research
»Transcriptomics: Open Access
»Trauma & Treatment
»Tropical Diseases
»Tropical Medicine and Surgery
»Tourism & Hospitality
  
V
»Vaccines & Vaccination
»Vascular Medicine & surgery
»Veterinary Science & Technology
»Virology & Mycology
»Vitamins & Minerals
»Vortex Science and Technology
  
W
»Women's Health Care
  
Y
»Yoga & Physical Therapy
 
   Browse by Subjects
Clinical
» AIDS & Clinical Research
» Anesthesia & Clinical Research
» Angiology
» Cancer Science & Therapy
» Carcinogenesis & Mutagenesis
» Cell Science & Therapy
» Chemotherapy
» Child & Adolescent Behavior
» Clinical & Cellular Immunology
» Clinical Case Reports
» Clinical & Experimental Cardiology
» Clinical & Experimental Dermatology Research
» Clinical & Experimental Ophthalmology
» Clinical & Experimental Pharmacology
» Clinical & Experimental Pathology
» Clinical Microbiology: Open Access
» Clinical Research & Bioethics
» Clinical Research on Foot & Ankle
» Clinical Toxicology
» Clinical Trials
»Clinics in Mother and Child Health
» Communication Disorders, Deaf Studies & Hearing Aids
» Cytology & Histology
» Forensic Research
»Forensic Biomechanics
» Integrative Oncology
»Immunome Research
»JBR Journal of Clinical Diagnosis and Research
» Neurology & Neurophysiology
» Pulmonary & Respiratory Medicine
» Stem Cell Research & Therapy
» Transplantation Technologies & Research
   
Pharmaceutical Sciences
» Advances in Pharmacoepidemiology & Drug Safety
» Alcoholism and Drug Dependence
» Bioanalysis & Biomedicine
» Biochemical Pharmacology
» Bioequivalence & Bioavailability
» Cardiovascular Pharmacology: Open Access
» Clinical Pharmacology & Biopharmaceutics
» Developing Drugs
» Drug Designing
» Drug Metabolism & Toxicology
» Medicinal & Aromatic Plants
» Molecular Pharmaceutics & Organic Process Research
» Pharmaceutica Analytica Acta
» Pharmaceutical Regulatory Affairs
» Pharmacovigilance
» Vaccines & Vaccination
   
Chemistry
» Advanced Chemical Engineering
» Analytical & Bioanalytical Techniques
» Chemical Sciences Journal
» Chromatography & Separation Techniques
» Medicinal Chemistry
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» Natural Products Chemistry & Research
» Organic Chemistry
» Physical Chemistry & Biophysics
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» Thermodynamics & Catalysis
» Theoretical and Computational Chemistry:Open Access
   
Environmental
» Anthropology
» Aquaculture Research & Development
» Astrobiology & Outreach
» Biodiversity & Endangered Species
» Earth Science & Climatic Change
» Ecosystem & Ecography
» Environmental & Analytical Toxicology
» Fisheries & Livestock Production
»Fundamentals of Renewable Energy and Applications
» Geography & Natural Disasters
» Hydrology: Current Research
»Innovative Energy Policies
»International Journal of waste resources
» Oceanography-Open Access
» Petroleum & Environmental Biotechnology
» Pollution Effects & Control
» Poultry, Fisheries & Wildlife Sciences
   
Omics
» Data Mining in Genomics & Proteomics
»Ergonomics
» Glycomics & Lipidomics
» Health & Medical Informatics
»JBR Journal of Young Scientist
» Metabolomics:Open Access
» OMICS Journal of Radiology
» Pharmacogenomics & Pharmacoproteomics
» Phylogenetics & Evolutionary Biology
» Proteomics & Bioinformatics
» Transcriptomics
   
Life Sciences
» Advanced Techniques in Biology & Medicine
»Advancements in Genetic Engineering
»Advances in Crop Science and Technology
»Advances in Dairy Research
» Aging Science
» Agrotechnology
» Air & Water Borne Diseases
» Antivirals & Antiretrovirals
» Autism-Open Access
» Bacteriology & Parasitology
» Biochemistry & Physiology
» Biochemistry and Analytical Biochemistry
» Bioenergetics
» Bioengineering & Biomedical Science
» Biofertilizers & Biopesticides
» Biological Systems
» Biometrics & Biostatistics
»Biomimetics Biomaterials and Tissue Engineering
» Biomolecular Research & Therapeutics
» Bioremediation & Biodegradation
» Biosafety
» Biosafety & Health Education
» Biosensors & Bioelectronics
» Biosensors Journal
» Biotechnology & Biomaterials
» Bioterrorism & Biodefense
» Cell & Developmental Biology
» Current Synthetic & Systems Biology
» Entomology, Ornithology & Herpetology
» Enzyme Engineering
» Fermentation Technology
» Fertilization: In Vitro - IVF-Worldwide
» Fisheries and Aquaculture Journal
» Forest Research
» Fungal Genomics & Biology
» Gene Technology
» Glycobiology
» Horticulture
» Homeopathy & Ayurvedic Medicine
»International Journal of Swarm Intelligence and Evolutionary Computation
» Marine Science: Research & Development
» Membrane Science & Technology
» Microbial & Biochemical Technology
» Molecular Biology
» Molecular Imaging & Dynamics
» Nanomedicine & Biotherapeutic Discovery
» Nanomedicine & Nanotechnology
» Nutrition & Food Sciences
» Plant Pathology & Microbiology
» Primatology
» Probiotics & Health
» Rice Research: Open Access
» Single Cell Biology
» Sociology and Criminology-Open Access
» Tissue Science & Engineering
» Tropical Diseases
» Veterinary Science & Technology
» Vitamins & Minerals
»Virology & Mycology
   
Engineering
» Advances in Automobile Engineering
» Advances in Robotics & Automation
» Aeronautics & Aerospace Engineering
» Applied & Computational Mathematics
» Applied Mechanical Engineering
» Architectural Engineering Technology
» Astrophysics & Aerospace technology
» Biochips & Tissue Chips
» Bioprocessing & Biotechniques
» Chemical Engineering & Process Technology
» Civil & Environmental Engineering
» Computer Science & Systems Biology
» Electrical & Electronics
» Food Processing & Technology
» Geology and Geosciences
» Geophysics & Remote sensing
»Global Journal of Technology and Optimization
» Industrial Engineering & Management
» Information Technology & Software Engineering
» International Journal of Advance Innovations, Thoughts & Ideas
»International Journal of Sensor Networks and Data Communications
» Irrigation and Drainage Systems Engineering
»Generalized Lie Theory and Applications
» Lovotics
» Material Sciences & Engineering
»Physical Mathematics
» Powder Metallurgy & Mining
» Telecommunications System & Management
» Textile Science & Engineering
»Vortex Science and Technology
   
Medical Sciences
» Addiction Research & Therapy
» Allergy & Therapy
» Alternative & Integrative Medicine
» Alzheimers Disease & Parkinsonism
» Anaplastology
» Anatomy & Physiology
» Ancient Diseases & Preventive Remedies
» Andrology
» Arthritis
» Autacoids
»Automatic Control of Physiological State and Function
» Bioceramics Development and Applications
» Biology and Medicine
» Biomusical Engineering
» Blood & Lymph
» Blood Disorders & Transfusion
» Bone Marrow Research
» Brain Disorders & Therapy
» Cardiovascular Diseases & Diagnosis
» Cloning & Transgenesis
» Community Medicine & Health Education
» Dentistry
» Depression and Anxiety
» Diabetes & Metabolism
» Emergency Medicine
» Endocrinology & Metabolic Syndrome
» Epidemiology: Open Access
» Family Medicine & Medical Science Research
» Gastrointestinal & Digestive System
» General Medicine
» General Practice
» Genetic Syndromes & Gene Therapy
» Gynecology& Obstetrics
» Gerontology & Geriatrics Research
» Hematology & Thromboembolic Diseases
» Hair: Therapy & Transplantation
» Health Care : Current Reviews
» Hereditary Genetics
» Human Genetics & Embryology
» Hypertension-Open Access
» Infectious Diseases & Therapy
» International Journal of Genomic Medicine
» Internal Medicine
»International Journal of Biomedical Data Mining
» International Journal of Physical Medicine & Rehabilitation
»JBR Journal of Interdisciplinary Medicine and Dental Science
» Leukemia
» Liver
»Malaria Chemotherapy, Control & Elimination
» Medical & Surgical Urology
» Medical Diagnostic Methods
» Medical Microbiology & Diagnosis
» Metabolic Syndrome
» Molecular Biomarkers & Diagnosis
» Molecular and Genetic Medicine
» Mycobacterial Diseases
» Neonatal Biology
» Nephrology & Therapeutics
»Neuroinfectious Diseases
» Neurological Disorders
» Novel Physiotherapies
» Nuclear Medicine & Radiation Therapy
» Nursing & Care
» Nutritional Disorders & Therapy
» Obesity & Weight Loss Therapy
» Occupational Medicine & Health Affairs
» Oral Health and Dental Management
» Oral Hygiene & Health
» Orthopedic & Muscular System
» Osteoporosis & Physical Activity
» Otolaryngology
» Pain & Relief
» Palliative Care & Medicine
» Pancreatic Disorders & Therapy
» Pediatrics & Therapeutics
» Primary Health Care
» Psychological Abnormalities in Children
» Psychology & Psychotherapy
» Reproductive System & Sexual Disorders
»Research and Development
» Rheumatology: Current Research
» Sleep Disorders & Therapy
» Spine
» Sports Medicine & Doping Studies
» Steroids & Hormonal Science
» Surgery: Current Research
» Thyroid Disorders & Therapy
» Translational Medicine
» Trauma & Treatment
» Tropical Medicine and Surgery
» Vascular Medicine & surgery
» Women's Health Care
» Yoga & Physical Therapy
 
Management
» Accounting & Marketing
» Arabian Journal Business and Management Review
» Arts and Social Sciences Journal
» Business and Economics Journal
» Business and Financial Affairs
» Civil & Legal Sciences
» Defense Management
» Entrepreneurship & Organization Management
» Global Economics
» Hotel & Business Management
» Intellectual Property Rights: Open Access
»International Journal of Accounting Research
» International Journal of Economics & Management Sciences
» Mass Communication & Journalism
» political Sciences & public affairs
»Review of Public Adminstration and Management
» Socialomics
» Stock & Forex Trading
» Tourism & Hospitality
 
   Conferences
Upcoming Conferences
»3rd International Conference and Exhibition on Biosensors & Bioelectronics August 11-13, 2014 San Antonio, USA
»2nd World Associations Congress August 11-13, 2014 San Antonio, USA
»International Meeting on Space- Open Debate August 12-13, 2014 San Antonio, USA
»5th International Conference and Exhibition on Analytical & Bioanalytical Techniques August 18-20, 2014 Beijing, China
»2nd International Conference on Epidemiology and Evolutionary Genetics August 18-19, 2014 Beijing, China
»2nd International Conference and Exhibition on Pharmacognosy, Phytochemistry & Natural Products August 25-27, 2014 Beijing, China
»2nd International Conference and Exhibition on Traditional & Alternative Medicine August 25-26, 2014 Beijing, China
»2nd International Conference and Exhibition on Mechanical & Aerospace Engineering September 08-10, 2014 Philadelphia, USA
»2nd International Conference and Exhibition on Lasers, Optics & Photonics September 08-10, 2014 Philadelphia, USA
»3rd International Conference and Exhibition on Neurology & Therapeutics September 08-10, 2014 Philadelphia, USA
»4th International Conference on Pharmaceutical Regulatory Affairs September 08-10, 2014 Raleigh, USA
»2nd International Conference on Radiology and Imaging September 08-09, 2014 Raleigh, USA
»2nd International Conference on Genomics & PharmacogenomicsSeptember 08-09, 2014 Raleigh, USA
»2nd International Conference on Alzheimer's Disease and Dementia September 23-25, 2014 Valencia Convention Centre, Valencia, Spain
»3rd International Conference and Exhibition on Nutrition & Food Sciences September 23-25, 2014 Valencia, Spain
»3rd International Conference on Clinical Microbiology & Microbial Genomics September 24-26, 2014 Valencia, Spain
»3rd International Conference on Tissue Science & Regenerative Medicine September 24-26, 2014 Valencia, Spain
»4th International Conference on Vaccines & Vaccination September 24-26, 2014 Valencia, Spain
»3rd International Summit on GMP, GCP & Quality Control September 25-26, 2014 Valencia, Spain
»5th World Congress on Bioequivalence and Bioavailability: Pharmaceutical R&D Summit September 29-October 01, 2014 Baltimore, USA
»2nd International Conference on Hematology & Blood Disorders September 29-October 01, 2014 Baltimore, USA
»3rd International Conference and Exhibition on Clinical & Cellular Immunology September 29-October 01, 2014 Baltimore, USA
»3rd International Conference and Exhibition on Materials Science & Engineering October 06-08, 2014 San Antonio, USA
»3rd International Conference on Forensic Research and Technology October 06-08, 2014 San Antonio, USA
»4th World Congress on Virology October 06-08, 2014 San Antonio, USA
»2nd International Conference on Endocrinology October 20-22, 2014 Chicago, USA
»3rd 3rd International Summit on Toxicology & Applied Pharmacology October 20-22, 2014 Chicago, USA
»3rd 4th World Congress on Cancer Science and Therapy October 20-22, 2014 Chicago, USA
»3rd 3rd International Conference and Exhibition on Cell & Gene Therapy October 27-29, 2014 Las Vegas, USA
»2nd International Conference on HIV/AIDS, STDs & STIs October 27-29, 2014 Chicago, USA
»2nd World Congress on Petrochemistry and Chemical Engineering October 27-29, 2014 Las Vegas, USA
»3rd International Conference and Exhibition on Pharmacovigilance & Clinical Trials October 27-29, 2014 Hyderabad, India
»3rd International Conference and Exhibition on Biowaivers and Biosimilars October 27-29, 2014 Hyderabad, India
»3rd International Conference on Translational Medicine November 03-05, 2014 Las Vegas, USA
»2nd International Conference on Predictive, Preventive and Personalized Medicine & Molecular Diagnostics November 03-05, 2014 Las Vegas, USA
»5th International Conference on Diabetes & Metabolism November 03-05, 2014 Las Vegas, USA
»2nd International Congress on Bacteriology and Infectious Diseases November 17-19, 2014 Chicago, USA
»2nd International Conference on Nursing & Healthcare November 17-19, 2014 Chicago, USA
»3rd International Conference on Surgery and Anesthesia November 17-19, 2014 Chicago, USA
»4th International Conference on Nanotek & Expo December 01-03, 2014 San Francisco, USA
»3rd International Conference and Exhibition on Obesity & Weight Management December 01-03, 2014 San Francisco, USA
»2nd International Summit on Clinical PharmacyDecember 02-03, 2014 San Francisco, USA
»3rd International Conference on Medicinal Chemistry & Computer Aided Drug Designing December 08-10, 2014 San Francisco, USA
»3rd International Conference and Exhibition on Probiotics & Functional Foods December 08-10, 2014 San Francisco, USA
Previous Conferences Organized/Co-organized
»Health Informatics & Technology Conference July 28-29, 2014 Baltimore, USA
»3rd International Conference on Gastroenterology & Urology July 28-30, 2014 San Francisco, USA
»3rd International Conference on Earth Science & Climate Change July 28-30, 2014 San Francisco, USA
»3rd International Conference and Exhibition on Orthopedics & Rheumatology July 28-30, 2014 San Francisco, USA
»International Conference on Business Economics of Broadcasting Media & Film Industry July 28-30, 2014, Baltimore, USA
»4th International Conference on Proteomics & Bioinformatics August 04-06, 2014 Chicago, USA
»3rd International Conference and Exhibition on Addiction Research & Therapy August 04-06, 2014 Chicago, USA
»2nd International Conference on Integrative Biology Summit August 04-05, 2014 Chicago, USA
»3rd International Conference and Exhibition on Cosmetology & Trichology July 21-23, 2014 Las Vegas, USA
»3rd International Conference and Exhibition on Food Processing & Technology July 21-23, 2014 Las Vegas, USA
»2nd International Conference on Oceanography July 21-23 , 2014 Las Vegas USA
»4th International Conference on Clinical & Experimental Ophthalmology July 14-16, 2014 Baltimore, USA
»3rd International Conference & Exhibition on Biometrics & Biostatistics July 14-16, 2014 Baltimore, USA
»2nd International Conference and Exhibition on Physical Medicine & Rehabilitation July 14-16, 2014 Baltimore, USA
»International Conference on Geriatrics & Gerentology July 08-10, 2014 Chicago , USA
»International Conference on Women's Health, Gynecology & Obstetrics July 08-10, 2014 Chicago, USA
»International Conference on Computer Graphics and Media Design July 08-10, 2014 Chicago, USA
»4th International Conference on Clinical & Experimental Cardiology April 14-16, 2014 San Antonio, USA
»4th International Conference on Clinical & Experimental Dermatology April 14-16, 2014 San Antonio, USA
»3rd International Conference and Exhibition on Pathology April 14-16, 2014 San Antonio, USA
»5th International Conference on Biomarkers and Clinical Research April 15-17, 2014 University of Oxford, UK
»2nd International Conference on Business Economics and Management April 21-23, 2014 Dubai, UAE
»2nd International Conference on Dental and Oral Health April 21-23, 2014 Dubai, UAE
»4th World Congress on Cell Science & Stem Cell Research June 24-26, 2014 Valencia, Spain
»3rd International Conference on Biodiversity & Sustainable Energy Development June 24-26, 2014 Valencia, Spain
»3rd International Conference and Exhibition on Occupational Health & Safety June 24-25, 2014 Valencia, Spain
»5th World congress on Biotechnology June 25-27, 2014 Valencia, Spain
»3rd International Conference on Nephrology & Therapeutics June 26-27, 2014 Valencia, Spain
»2nd International Conference on Bioprocess and Engineering June 26-27, 2014 Valencia, Spain
»2nd International Conference on Dental and Oral Health April 21-23, 2014 Dubai, UAE
»5th International Conference on Biomarkers and Clinical Research April 15-17, 2014 University of Oxford, UK
»3rd International Conference and Exhibition on Pathology April 14-16, 2014 San Antonio, USA
»4th International Conference on Clinical & Experimental Dermatology April 14-16, 2014 San Antonio, USA
»4th International Conference on Clinical & Experimental Cardiology April 14-16, 2014 San Antonio, USA
»4th International Conference and Exhibition on Pharmaceutics & Novel Drug Delivery Systems March 24-26, 2014 San Antonio, USA
»3rd International Conference and Exhibition on Metabolomics & Systems Biology March 24-26, 2014 San Antonio, USA
»2nd International Conference on Agricultural & Horticultural Sciences, February 03-05, 2014 Hyderabad, India
»International Conference and Exhibition on Traditional & Alternative Medicine, December 09-11, 2013 Hyderabad, India
»2nd International Conference and Exhibition on Obesity & Weight Management, December 02-04, 2013 Las Vegas, USA
»International Conference on Nursing & Emergency Medicine, December 02-04, 2013 Las Vegas, USA
»3rd International Conference on Nanotek & Expo, December 02-04, 2013 Las Vegas, USA
»3rd World Congress on Virology, November, 20-22, 2013 Baltimore, USA
»International Congress on Bacteriology and Infectious diseases, November 20-22, 2013 Baltimore, USA
»3rd World Congress on Cell Science & Stem Cell Research, November 20-22, 2013 San Antonio, USA
»2nd International Conference and Exhibition on Pharmacovigilance & Clinical Trials, November 18-19, 2013 San Antonio, USA
»International Summit on Clinical Pharmacy & Dispensing, November 18-20, 2013 San Antonio, USA
»World Congress on Petrochemistry and Chemical Engineering, November 18-20, 2013 San Antonio, USA
»International Conference on Functional and Comparative Genomics & Pharmacogenomics, November 12-14, 2013 Chicago, USA
»2nd International Conference and Exhibition on Cosmetology & Trichology, November 12-14, 2013 Chicago, USA
»2nd International Summit on GMP, QA & QC, November 12-14, 2013 Chicago, USA
»2nd International Summit on GLP, GCP & Clinical Pharmacology, November 12-14, 2013 Chicago, USA
» International Conference on Fermentation Technology, Bioprocess and Cell Culture, October 28-30, 2013 Kansas City, USA
»2nd International Conference and Exhibition on Food Processing & Technology, October 28-30, 2013 Kansas City, USA
»International Conference on HIV/AIDS, STDs, & STIs, October 24-25, 2013 Orlando-FL, USA
»2nd International Conference and Exhibition on Cell & Gene Therapy, October 23-25, 2013 Orlando, USA
»2nd International Conference and Exhibition on Probiotics & Functional Foods, October 23-25, 2013 Orlando, USA
»International Conference and Exhibition on Pharmacognosy, Phytochemistry and Natural Products, October 21-23, 2013 Hyderabad, India
» 3rd World Congress on Cancer Science & Therapy, October 21-23, 2013 California, USA
»3rd International Conference on Pharmaceutical Regulatory Affairs, October 21-23, 2013 California, USA
»2nd International Conference on Clinical & Cellular Immunology, October 15-17, 2013 Las Vegas, USA
»2nd International Conference on Medicinal Chemistry & Computer Aided Drug Designing, October 15-17, 2013 Las Vegas, USA
»4th International Conference and Exhibition on Analytical & Bioanalytical Techniques, October 15-17, 2013 Las Vegas, USA
»2nd International Summit on Toxicology, October 07-09, 2013 Las Vegas, USA
»International Conference and Exhibition on Lasers, Optics & Photonics, October 7-9, 2013 San Antonio, USA
»2nd International Conference and Exhibition on Materials Science & Engineering, October 07-09, 2013 Las Vegas, USA
»2nd International Conference on Forensic Research & Technology, October 07-09, 2013 Las Vegas, USA
»International Conference and Exhibition on Biochemical & Molecular Engineering, October 07-08, 2013 San Antonio, USA
»International Conference on Psychology, Autism and Alzheimer's Disease, September 30-October 01, 2013 San Antonio, USA
»International Conference and Exhibition on Mechanical & Aerospace Engineering, September 30-October 02, 2013 San Antonio, USA
»2nd International Conference and Exhibition on Biowaivers & Biosimilars, September 23-25, 2013 Raleigh, USA
»4th World Congress on Biotechnology, September 23-25, 2013 Raliegh, USA
»International Conference on Hematology & Blood Disorders, September 23-25, 2013 Raliegh, USA
»2nd International Conference on Surgery and Anesthesia, September 16-18, 2013 Las Vegas, USA
»2nd International Conference on Clinical Microbiology & Microbial Genomics, September 16-18, 2013 Las Vegas, USA
» International Conference on Omics Studies, September 04-06, 2013 Orlando-FL, USA
»International Symposia on Entomology, September 04-06, 2013 Miami, USA
» World Congress on Endocrinology, August 26-28, 2013 Raleigh, USA
»2nd International Conference on Hydrology and Groundwater Expo, August 26-27, 2013 Raleigh, USA
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Journal Details
 
 
Review Article Open Access
Role of Chemokines and Chemokine Receptors in Prostate Cancer Development and Progression
1Department of Urology, Miller School of Medicine, University of Miami, Miami, FL 33136, USA
2Veterans Administration Miami Hospital, Miami, Florida, USA
3Cell Signaling and Tumor Angiogenesis Laboratory, Department of Genetics, Boys Town National Research Hospital, Omaha, NE 68131, USA
4Department of Biomedical Sciences, Creighton University School of Medicine, Omaha, NE 68131, USA
5Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA
*Corresponding author: Dr. Rajendra K Singh,
Department of Urology, Miller School of Medicine,
University of Miami, Miami,
FL 33136 USA,
Tel: (305) 243-1017,
Fax: (305) 243-9724,
E-mail: rsingh2@med.miami.edu
 
Received May 11, 2010; Accepted June 02, 2010; Published July 02, 2010
 
Citation: Singh RK, Sudhakar A, Lokeshwar BL (2010) Role of Chemokines and Chemokine Receptors in Prostate Cancer Development and Progression. J Cancer Sci Ther 2: 094-099. doi:10.4172/1948-5956.1000031
 
Copyright: 2010 Singh RK, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
 
Abstract
 
Prostate cancer (PC) is the second leading cause of cancer deaths in men in America and Western Europe. Epidemiological studies suggest that prostate cancer incidence increased in last few years in Asian population. The causes or consequences of increasing trend of prostate cancer incidence are not completely known. Emerging evidences suggest that among the many risk factors, inflammation is the major risk factor for developing prostate cancer and its progression to metastasis. It is proposed that exposure to environmental factors such as infectious agents, dietary agents and saturated lipids leads to injury of the prostate due to chronic inflammation and regenerative risk factor lesions referred to as proliferative inflammatory atrophy (PIA). These phenomena predominantly control by a number of proinflammatory macro molecules such as chemokines, and their receptors. Some recent studies suggest that many of these pro-inflammatory chemokines and their receptors are the products of protooncogenes or tumor suppressor pathways in many cancers including that of the prostate. This review article will focus on the current biology of chemokines and chemokine receptors pathways in genesis of prostate cancer. An understanding of this axis may enable researchers to develop targeted strategies for prostate cancer. 
 
Introduction
 
Prostate cancer (PC) represents the second leading cause of death among all cancer types in men in Europe and North America (Collin et al., 2008). Emerging evidences suggest that among the many risk factors, inflammation is a major risk factor for developing prostate cancer and its progression to metastasis (De Marzo et al., 2007). The pro-inflammatory regulators such as chemokines and their receptors network seem to play crucial functions in prostate tumorigenesis, although chemokines have been thought of primarily as leukocyte attractants. In general, the function of chemokines is to arrest leukocytes at inflamed blood vessels and guide to lead them to specific sites of inflammation. Due to specific function of site-specific homing for leukocytes from inflammatory sites, these mediators may play several key steps of prostate carcinogenesis including production of inflammatory cells. Chronic inflammation predisposes cells to produce dysregulated amounts of chemokines for malignant transformation and progression. The accumulating evidence also points to a direct effect of chemokines on cancer cells that express chemokine receptors. In particular, some chemokines can activate anti-apoptotic pathways in cancer cells (Singh and Lokeshwar, 2009). By either mechanism, tumor cells that secrete and/or respond to chemokines would have a selective advantage. It is extensively documented in number of studies that they contribute to a number of tumor-related processes, such as tumor cell growth, Araki et al., 2007angiogenesis/angiostasis, local invasion, and metastasis in many tumor types including prostate (Singh and Lokeshwar, 2009; Bingle et al., 2006; Papetti and Herman, 2002). Specifically members of the chemoattractant chemokines, more popularly known as CXC chemokines, and their receptors are significant players in several of the critical steps in tumorigenesis and/or metastasis (Singh et al., 2007; Vicari and Caux, 2002; Zlotnik, 2004; Murakami et al., 2004). Many studies mentioned that they have been shown to play potentially important roles in many of the critical steps of the androgen independent and metastasis process. For example CXC chemokine CXCL-8 (IL-8) plays multiple roles in transition of androgen sensitive tumor cells to androgen insensitive, drug resistance in prostate cancer cells (Tanaka et al., 2005; ). A recent report indicates that inhibition of IL-8 in vitro inhibits cell survival signaling of Akt and bcl2 in prostate cancer cells (Singh and Lokeshwar, 2009). Several other chemokines produced by primary prostate tumor site and in distant metastasis locations are shown to play significant role in prostate tumorigenesis (Waugh et al., 2008). These wide and differential distributions of chemokines and their receptors particularly account for the pleiotropic actions of chemokines in PC, including the modulation of growth, angiogenesis, invasion, and metastasis (Vindrieux et al., 2009; Tanaka et al., 2005; Singh et al., 2007; Ben-Baruch, 2008).
 
The known function of chemokines in other aspects of biology or human diseases, apart from cancer, has been detailed in several other reviews (Rossi and Zlotnik, 2000; Gerard and Rollins, 2001; Aragon-Ching et al., 2010). This review will emphasize what we believe are striking about the roles of selected chemokines in the inflammatory responses to prostate cancer initiation to metastasis process. This review will also highlight some of the similarities between the functions of chemokine receptors in physiologic homing of leukocytes and purposed roles for these receptors in prostate cancer progression and metastasis. Therefore, this review will include descriptions of possible concurrent roles in inflammation and prostate tumorigenesis. Within the space of this review, it is not possible to discuss all the available evidence regarding roles for a specific chemokine and chemokine receptors networks in details. Thus, a referenced summary of possible roles for some important chemokine receptors in prostate cancer is discussed. With the development of specific chemokine receptor antagonists, it may be possible to exploit the vulnerability of cancer cells by disrupting chemokine receptor-mediated signaling and directly inhibit prostate tumor growth or render tumor cells more susceptible to traditional anticancer treatment modalities. This review will focus on the roles and the mechanisms of action and regulation of chemokines in the different steps of PC development and will discuss present literature on the novel strategies that are currently envisioned to target chemokines in PC.
 
Prostate cancer
 
Adenocarcinoma of the prostate is the most common malignancy of the male genitourinary tract and is a significant health problem. The 2.4 million people living with PC, 214000 new cases per year and estimated 27000 death occurred in the United States in 2008 (Jemal et al., 2008). Localized prostate carcinomas exist in most of elderly males at the time of diagonosis, but the most of those carcinomas are asymptomatic and are medically important (Denberg et al., 2006; Giovannucci et al., 2007; Mazur and Merz, 1996; Pienta and Loberg, 2005). For this reason, the research of tumor proliferation and dissemination are even more important of this disease than of other cancers.
 
The most commonly used method to diagnose and evaluate prostate cancer is the PSA (Prostate Specific Antigen) test though it is far from perfect. The only test which can fully confirm the diagnosis of prostate cancer is a biopsy. The recent European Randomized Study of Screening for Prostate Cancer suggests that risks incurred by screening, diagnosis (Schröder et al., 2009; Koukourakis et al., 2009; Aus et al., 1996) and resulting treatment (Rietbergen et al., 1997; Yao and Lu-Yao, 1999; Alibhai et al., 2005; Potosky et al., 2004; Lim et al., 1995; Hamilton et al., 2001; Fowler et al., 2002) of prostate cancer are both substantial and well documented in the literature. To the extent that over diagnosis occurs with prostatecancer screening, many of these risks occur in men in whom prostate cancer would not have been detected in their lifetime and were clinically irrelevant (Tsai et al., 2007). Treatment for prostate cancer includes surgery, radiation therapy, cryosurgery and total androgen deprivation (hormonal) therapy. Surgical removal of the prostate (also called prostatectomy) is a common treatment mainly for early stage prostate cancer. Radiotherapy is also widely used in prostate cancer treatment. However, once the tumor has spread, such local tumor removal has little impact on the overall outcome or course of disease (Jongsma et al., 2002). Thus, the disseminated tumors need innovative and systemic approaches. Early in the prostate carcinoma, such physical or chemical castration (anti-androgen) leads to regression of the tumor masses (Jin et al., 2004). However, this rarely cures prostate cancer as androgen independence develops within a year or two (Nacusi and Tindall, 2009). Thus, focus on the tumor-intrinsic events, predominantly mediated by chemokines and chemokine-receptors in androgen-independent prostate carcinomas, as novel approaches to halting the progression of this disease. In the following sections we will discuss the importance of these molecular pathways in the development and progression of PC and the therapeutic significance of the inhibition of these of pro-inflammatory signals. 
 
Chemokines
 
The chemokines represent a large group of small secreted proteins (8–11 kDa in size), which are grouped into four families (C, CC, CXC, and CX3C) based on the spacing of key cysteine residues near the N-terminus of these proteins. The CC and CXC families represent the bulk of known chemokines (currently 53) (Zlotnik and Yoshie, 2000). Most of the chemokines are divided between the CC and CXC classes. There are only two known C chemokines, and one known CX3C chemokine. Several CC chemokines with six cysteines have been discovered, defining a structural subclass relative to the more numerous group of CC chemokines with four cysteines. The CXC class can also be divided into two subclasses, ELR+ and ELR-, depending on whether the tripeptide signature glu-leu-arg is found N-terminal to the first cysteine (Zlotnik and Yoshie, 2000).
 
Chemokines are primarily known in the regulation of the motility of hematopoietic cells (immune system cells) and their ability to stimulate directional migration of nearly all classes of leukocytes during inflammation through the activation of a group of cell surface receptors belongs to G-protein receptors family (Ruffini et al., 2007). Neutrophils, for example, migrate strongly in response to chemokines such as CXCL8 (interleukin-8) and eosinophils to CC chemokine ligand 11 (CCL11; eotaxin). Some chemokines have been expressed to specific cell types (Zlotnik and Yoshie, 2000). Many epithelial cell types and macrophages for examples, produce significant levels of chemokines. These cell populations can have an immediate impact on the environment tumor. The CXC chemokines mostly ELR+ are angiogenic. These include CXCL8 (IL-8), epithelial-neutrophil activating protein (ENA-78) and growthrelated genes (GRO-α, GRO-β, GRO-γ and GCP-2), and several other neutrophil activating proteins (Brat et al., 2005). The second group of CXC chemokines, which lack the ELR motif, include interferon-γ- inducible protein (IP-10), monokine induced by γ-interferon (MIG) and stromal derived factor (SDF-1) (Ogawa et al., 2002) Most of these ELR-negative CXC chemokines, have been shown to antagonize the angiogenic activities of the ELR-positive CXC chemokines as well as basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) (Moore et al., 1999). It is still not clear, however, whether all of these chemokines contribute cancer related chemotaxis, or whether a specific chemokine mediates the bulk of the chemotactic activity and can be targeted for therapy. Chemokine biology is also central to the immunologic anti-tumor response through the recruitment of effector lymphocytes and the subsequent regulation of their effector function within tumor environments (Homey et al., 2002). Data from breast carcinoma studies have suggested that the specific effects mediated through chemokines could be significantly different depending on the source of ligand or receptor expression (Azenshtein et al., 2002). 
 
Chemokine receptor
 
Chemokines interact with cell-surface receptors, which are members of a large superfamily their of seven-transmembrane domain, G protein-coupled receptors. The receptor nomenclature system is based on the observation that ligand selectivity of promiscuous chemokine receptors is restricted by chemokine class. Some chemokine receptors bind to multiple chemokines and vice versa, suggesting that certain redundancies exist in chemokine function. There are 18 human chemokine receptors (Zaballos et al., 1999; Homey et al., 2000; Schweickart et al., 2000; Yoshida et al., 1998) and over fifty distinct chemokines identified at present .They play very distinct role in normal cells and cancer (Zlotnik and Yoshie, 2000). The molecular mechanism of signaling function has still not been demonstrated for Duffy, D6, CCX CKR, and CXCR7 which are all 7TM proteins that bind large subsets of chemokines (Homey et al., 2000) The ten human chemokine receptors such as CXCR1, CXCR4, CXCR5, CXCR6, CCR6, CCR8, CCR9, CCR10, XCR1 and CX3CR1 are highly selective for one main high affinity endogenous chemokine ligand. On the other hand, other chemokine receptors (CXCR2, CXCR3 and CXCR7) are typically highly promiscuous. For example CXCR7 is member of chemokine receptors, CXC family, it has been later shown to bind a new two chemokines, CXCL12/SDF-1 and CXCL11 (Burns et al., 2006). The exact function of CXCR7 how it is regulated in prostate and other cancer is not known. 
 
The major function of chemokines is to regulate leukocyte trafficking in hematopoiesis and in innate and adaptive immunity in many cell types. Other functions include angiogenic activity, apoptosis, T-cell differentiation and phagocyte activation (Kim, 2004). Inadvertent activation of chemokine receptors leads to autoimmunity by inappropriately targeting self antigens for destruction by cytotoxic T-cells and macrophages (Christopherson and Hromas, 2001). They are sub classified according to their function such as homeostatic leukocyte homing molecules (CXCR4, CXCR5, CCR7, CCR9) versus inflammatory/inducible molecules (CXCR1, CXCR2, CXCR3, CCR1-6, CX3CR1), and substantial progress has been made, in part through the study of knock-out mice, in identifying specific phenotypes in development and disease. Phenotypes are concentrated in hematopoietic development, innate and adaptive immune responses and susceptibility to infectious agents (Cyster, 1999). Chemokine receptors preferentially expressed on important functional subsets of epithelial cells, dendritic cells, monocytes and lymphocytes have been defined in many studies (Charbonnier et al., 1999; Sallusto et al., 1998). 
 
Chemokines and chemokine receptors in inflammation, prostate cancer development and progression
 
Prostate Cancer (PC) progression is a complex physiological and pathological event. Several multidisciplinary studies have been suggesting a link between chronic inflammation and PC. Several studies suggest a link between bacterial infections, inflammation and pre-deposition of pro-inflammatory proteins in the prostate gland. Such self-perpetuating mechanism can be triggered with the age of men and may increase the risk of malignancy of prostate (Yanamandra et al., 2009; Hermani et al., 2006; Xie et al., 2010). Studies have also found an increased in relative risk of PC in men with a prior history of certain sexually transmitted infections or prostatitis diseases (Sadeghi-Nejad et al., 2010; Cheng et al., 2010). Significant association between prostatitis, sexually transmitted diseases (STDs), and prostate cancer among African American, Asian American, Latino, were found in participants of the California Men’s Health Study (Robert et al., 2009). Furthermore, several studies suggested genetic or germline defect or variants of several genes associated with the immunological aspects of inflammation in modulating PC risk (Vasto et al., 2008). Somatic alterations of genes are shown to be involved in defenses against inflammatory damage and in tissue recovery. Several studies showed that chronic inflammation of prostate area caused a novel putative PC precursor lesion called proliferative inflammatory atrophy, which shares some molecular traits with prostate intraepithelial neoplasia and PC (Sciarra et al., 2007). The hypothesis associating chronic inflammation and PC wastested in a number of animal models of prostate inflammation that should allowed the elucidation of the mechanisms by which prostatic inflammation could lead to the initiation and progression of PC (Nelson et al., 2001; Hsing and Chokkalingam, 2006). These emerging insights into chronic inflammation in the etiology of prostate carcinogenesis hold the promise of spawning new diagnostic and therapeutic modalities for men with PC (Wagenlehner et al., 2007; Chung et al., 2005). 
 
Prostate tumorigenesis occurs through several steps, the first being the transition from normal prostate to PIN in many cases (Yanamandra et al., 2009; Hermani et al., 2006), but not all BPH diseases establish cancer in later stage. During the transitions from normal to PIN and from PIN to PC, a number of chemokines and chemokine receptors display variations in their expression. It is most important to notice that chemokines are produced by a variety of cells such as tumor-associated fibroblasts, endothelial cells, or tumor infiltrating cells such as macrophages and or lymphocytes have selected advantage of progression of prostate disease. Many studies have been suggested that chemokines CXCL8, CXCL12, and CCL2 level increased with the progression of prostate PC. Expression of IL-8 is low levels in normal human prostate at the apical membrane of epithelial cells (Murphy et al., 2005). The levels of proangiogenic chemokine IL-8 is higher in PIN compared with normal prostate tissue and cell lines represent the PIN and stroma tissue of PIN. This suggests that a reactive stroma pattern is correlated with an increase in CXCL8 levels in the adjacent epithelium. 
 
It is suggested in many studies that many CXC chemokines are involved in prostate that tumor invasion and metastasis. This is very important mechanism of prostate tumor progression. The ability to break matrix barriers causes the vast majority of morbidity and mortality from prostate cancer due to metastasis to vital organs such as bone, liver and lymph nodes. Histological analyses in de-novo human tumor specimens and animal tumor models showed that cancer cells invading into adjacent healthy tissues or breaching a basement membrane to access a vessel for dissemination. Cell motility and invasion is tightly controlled by growth factors and cytokines during organogenesis, inflammation and wound healing, while it appears to become dysregulated during tumorgenesis. This lack of control and direction results in invasion. Prostate cancer cells that becomes hormone-independent become highly invasive with an increased incidence of skeletal/bone metastases as the disease progresses (Gladson and Welch, 2008; Bostwick et al., 2004; Logothetis and Lin, 2005). PC shares a number of features with benign prostatic hyperplasia (BPH) and the putative precursor of cancer, prostatic intraepithelial neoplasia. All three stages of prostate disease increase in prevalence with age and require androgens for growth and development. So far, the factors responsible for PC progression remain elusive. Among the mediators of carcinogenesis, the significance of chemokines in PC progression has increased. In multicellular organisms, the interactions between individual cells are essential to ensure their correct functions in an appropriate spatial and temporal manner. In particular, cell homing requires a fine tune in embryonic development, inflammation, or immunity. Such events appear to be deregulated in the neoplastic process. In the PC context and other cancer, chemokines play diverse effects and some of them deriving from their ability to induce cell migration and angigogenesis. The ability of chemokines to enhance the motility of leukocytes, endothelial cells, and by tumor cells is a key factor in determining the cancer establishment and progression. On the other hand, some chemokines may inhibit angogengesis and angiostatic effects. 
 
The expression level of chemokines is also altered with the progression of PC. In situ hybridization experiments have shown that CXCL8 RNA and its receptors CXCR1 and CXCR2 levels increase with the Gleason score of prostate tumors of high-grade tumors (Gladson and Welch, 2008). The localization of CXCL8 is somewhat controversial as another study has reported that CXCL8 is expressed by the neuroendocrine cells PC. This discrepancy could arise from the use of different antibodies to detect CXCL8. The same study also observed an increased expression of CXCR1 in epithelial cells of PC as compared with normal prostate. Moreover, CXCR2 is present in neuroendocrine cells. CXCL8 protein can also be detected in the serum of patients. Serum CXCL8 levels are elevated in patients Wangh et al., 2007 with bone metastasis compared with patients with localized disease. 
 
Some studies have suggested that chemokines and their receptors could also contribute to the variable incidence of PC in higher in African–American men when compared with European–American men. A comparative microarray analysis of chemokine expression profiles of patients with primary prostate tumors showed that CCL5, CCR7, and CXCR4 were expressed at higher levels in African–American patients compared with European–American patients (Wallace et al., 2008). Genetic polymorphism of some chemokine genes is altered in PC, which could potentially correlate with the expression levels of chemokines. A single nucleotide polymorphism of CXCL12 G801A has been reported. It appears that the genotype GA+AA is increased in PC patients compared with healthy controls (Hirata et al., 2007). In addition, the genotype AA is more frequent in metastatic patients compared with non-metastatic patients (Hendrix et al., 2000). The growing evidence of chemokine involvement in all stages of prostate cancer progression, manipulation of this signaling pathway may be therapeutic benefit. Several antagonist including AMD 3100 and T22 are tested but unlikely owing to pharmacokinetic problems (Hendrix et al., 2004; Civenni and Sommer, 2009). Apart from metastasis, increasing evidence suggest that chemokines is implicated in neoplastic cell transformation. Chemokines regulate proliferation and migration of various types of normal stem and progenitor cells, including precursor cells of neuroectodermal origin. Based on this it is conceivable that the established role of chemokines in cancer cell proliferation and organ-specific metastasis might also be associated with stem cell-like cells present in the tumor. Such cancer stem cells represent a small subpopulation of tumor cells that are thought to initiate and sustain tumor formation (Burger et al., 1999). The IL-8 and CXCL1 have been demonstrated to continually stimulate certain cells expressing the CXCR1 and CXCR2 by autocrine and paracine mechanism and leading to malignant and oncogenic transformation (Waugh et al., 2008). Clinical observations and mouse models have suggested that inflammation can be pro-tumorigenic properties such CXCL16 and CXCR6 arising in an inflammatory milieu and mediate pro-tumorigenic effects of inflammation through direct effects on cancer cell growth and by inducing the migration and proliferation of tumor-associated leukocytes (Darash-Yahana et al., 2009). The multi-faceted roles of chemokine and chemokine receptors in PC are outlined in Table 1
 
Table 1: Overview of Chemokines and Chemokine Receptors in Prostate Cancer.
 
Conclusion Remarks
 
Chemokines and chemokine-receptors seems to be important factors not only play a significant role in normal cell physiology but also regulated many tumor related mechanism such as increases cell survival and migration associated with metastasis of several cancers including prostate. Leukocyte infiltration is a cardinal feature of inflammation and important in progression of prostate cancer. This mechanism of up-regulation not only autocrine and paracrine mechanism of tumor cells secreted chemokines to promote tumorigenesis but also they responsible for eliciting local accumulation of inflammatory cells that appear to play a same role in the formation of peri- and intratumoural infiltrates. Chronic inflammation predisposes and scretion of tumor related chemokines (CXC) are likely to be important factors in prostate cancer formation and progression. In part, chemokines may be a consequence of its ability to attract mononuclear cells to cancer sites, where they provide growth or angiogenic factors that enhance cancer development. However, accumulating evidence also points to a direct effect of chemokines on cancer cells that express chemokine receptors. In particular, some chemokines can activate anti-apoptotic pathways in these cells. By either mechanism, tumor cells that secrete and/or respond to chemokines would have a selective advantage of host systems to promote tumorigenesis. 
 
Acknowledgements
 
This work was supported by grant from VA mert Review (VAMC 5312.1 to BLL) and Flight Attendant Medical Research Institute Young Clinical Scientist Award Grant (#062558) and #RO1CA143128, startup funds of Cell Signaling and Tumor Angiogenesis Laboratory at Boys Town National Research Hospital to AS. 
 
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