Primary Bone Tumors and its Advancement into 3D
Received: 01-Jul-2022 / Manuscript No. joo-22-70005 / PreQC No. joo-22-70005 (PQ) / Reviewed: 04-Jul-2022 / QC No. joo-22-70005 / Revised: 19-Jul-2022 / Manuscript No. joo-22-70005 (R) / Published Date: 22-Jul-2022 DOI: 10.4172/2472-016X.1000175
Abstract
Primary bone tumors, such as osteosarcoma, are highly aggressive pediatric tumors that develop lung metastases in 30% of cases and are characterized by a poor prognosis. Bone is also the third most common metastatic site in patients with advanced cancer, and when tumor cells settle in the skeleton, the disease is usually considered incurable and treatment is palliative. Osteosarcoma and bone metastases share a niche with the microenvironment of the same tissue. 3D culture is a new and promising approach for studying the interaction of tumor cells with other cells or cell-free components of the tumor microenvironment (fibroblasts, mesenchymal stem cells, bone ECM, etc.). In fact, 3D models can mimic the physiological interactions that are important for regulating soluble paraclinic factor response, tumor drug resistance, and aggression, and overall, these innovative models are animal-based. It may be possible to avoid the use of preclinical cancer models. So far, static and dynamic 3D cell culture models have proven to be particularly suitable for screening anticancer agents, providing accurate information by transforming in vitro cell cultures into precision medicine. This short report summarizes the latest technologies in the field of primary and metastatic bone tumors, the various methods and techniques used to realize 3D cell culture systems, and the path to personalized medicine.
Keywords
Bone tumors; Microenvironment; Fibroblasts; Cell culture
Introduction
Osteosarcoma is a mesenchymal disease. They are derived from bone, and mesenchymal stem cells (MSCs) are tumor-forming progenitor cells [1, 2] and are also stromal cells [3, 4] involved in tumor development. In bone, tumor-supporting stroma is formed by osteoblasts (bone-forming cells derived from MSC), osteolytic cells (bone-absorbing cells), endothelial and immune cells, and MSC. Osteoclasts attach to the bone surface and the range of factors involved in their activation may depend on the type of tumor. For example, osteoclasts can be stimulated directly by tumor cells [5, 6] or by tumorinduced osteoblasts [7]. In OS, the presence of osteoclasts in the tumor microenvironment may promote the behavior of osteoblasts in tumor cells and increase their aggression [8] and is considered a poor prognosis factor [9]. Similarly, in BM, a delicate balance between bone deposition and resorption forms a pathogenic process [10]. Given the complexity and heterogeneity of bone tumors, treatment strategies aimed at eradicating them show a consistent slowdown compared to many other carcinomas. A better understanding of osteosarcoma carcinogenesis is clearly needed to overcome drug resistance and improve low survival. Many disorders make it difficult to study bone cancer with current tools. These are effective for the physical difficulty of manipulating bone as tissue, the rarity of sarcoma tumors, the difficulty of obtaining tumor tissue fragments from human patients with BM, and human disease includes a limited number of models to mimic. For all these reasons, the need for a new cell model of osteosarcoma is becoming increasingly important. This review focused on cellular models currently available for BM or sarcoma research. There have been recent advances from 2D to 3D cell culture models to model multicellular systems. Three-dimensional architecture is one of the main themes based on the formation of tissues and organs. This complexity begins during embryogenesis and is increased by cell-cell contact, which is the basis of intracellular function [11]. In addition, the cells are surrounded by ECM. It is important in determining cell differentiation, proliferation and homeostasis [12]. Therefore, an ideal 3D culture model should not only properly mimic carcinogenesis and maintenance of tumor cell proliferation, but also mimic the interactions between mixed cells within the ECM. To date, several techniques have been developed and explored for this purpose. 3D static cultures include seeding of cells with a spherical structure that does not contain extracellular matrix, and seeding of cells into a matrix or scaffold made of natural or synthetic biomaterial. 3D dynamic cultures include bioreactor-cultured spheroids or scaffolds and cell dissemination on microfluidic perfusion devices.
Spheroids
One of the pioneering studies that opened the field of 3D culture is Sutherland et al. It is a study of [13]; they found that floating and proliferated lung cells were in the outer zone of proliferating cells, the malnourished and oxygenated intermediate zone with few mitotic cells, and the central zone of necrosis, which is a physiological feature. We first observed the formation of developing spheroids. Tumor mass forced levitation spheroids are the easiest way to generate spheroids. It prevents cells from adhering to the bottom of the well and provides buoyant aggregates and cell-cell contact. The hanging drop method is the most widely used and static technique [14]. Conversely, rotating cell culture bioreactors, spinner flasks, or agitated tank cultures [15] force uniform spheroid formation by continuous agitation [16]. Again, spheroids can be formed by a single cell type or mimic the interactions between multiple cells. B. Tumors and stromal cells [17]. These culture systems are highly reproducible and have low manufacturing costs. As early as 1971, it was clear that spheroids could be used for drug screening and radiation therapy testing [18] despite the benefits, not all cell lines form spheroids, and some just form unpredictable cell aggregates.
Matrices and Scaffolds
Similar to spheroids, cells seeded in a matrix or scaffold can be cultured in either static or dynamic culture using a rotating cell culture bioreactor. A hydrogel-based matrix is a network of hydrophilic, physically or chemically cross-linked polymer molecules that retain large amounts of water [19] and provide a 3D biomimetic environment that supports cell proliferation and differentiation. Masu [20] the great advantage of hydrogels is that they adapt to the specific properties of ECM. For example, hydrogels can be designed to contract or swell based on the environmental stimuli they receive [19] and can be easily concentrated with specific cell adhesion ligands to mimic soft tissue. Hydrogels are synthetic or naturally derived [21] and are primarily based on matrigel, collagen, or fibrin. Matrigel is derived from mouse sarcoma and has the most heterogeneous composition. The main components are structural proteins such as laminin, nidgen, collagen, and heparan sulfate proteoglycan. Matrigel polymerization is temperature dependent. Collagen-based hydrogels are also pHdependent and play an important role in cancer progression and are the most abundant protein in mammalian ECM. However, due to pH dependence, collagen-based hydrogels are unsuitable for studying the effects of tumor acidosis, a key feature in the development of bone cancer [22,23] or cancer-induced bone pain [24,25] will be 3D scaffolds, traditionally described as tools made from polymer biomaterials, provide attachment sites and hydrogel-like interstitial spaces for cells to grow and proliferate, thereby forming 3D structures. This has the advantage of providing a reproduction of the ECM [16]. Scaffold stiffness can be adjusted to affect cell adhesion, proliferation, and activation [26]. The materials used for scaffolding are biocompatible and must induce molecular biometric recognition of cells [27]. Biomaterials that mimic ECM are considered to be the most biocompatible, consisting of collagen, hyaluronic acid, matrigel, elastin, laminin-rich extracellular matrix, and alginate, chitosan, and silk. Synthetic biomaterials include two-phase systems such as polyethylene glycol, hyaluronic acid-PEG, polyvinyl alcohol, polycaprolactone, or polyethylene glycol-dextran. Many biomaterials, such as ceramics, can fall into the categories of natural or synthetic materials [28].
Microfluidic Device
Recent advances in tissue engineering have led to the development of living multicellular microculture systems that are maintained in a controllable microenvironment and function at organ-level complexity [29]. Applications of these “on-chip” technologies are becoming more and more popular in cancer research [30]. The importance of these systems is that continuous perfusion of the medium through the microfluidic network can mimic blood flow and exchange nutrients, oxygen, and metabolites that are important for modeling living cancerous tissue with blood tissue innovation [31]. Invading cells that detach from solid tumors are exposed to the new microenvironment of the circulatory system. Depending on the size of the blood vessel, blood flow velocity can reach 0.03-40 cm / s, arterial hemodynamic shear force is 4.0-30.0 dyne / cm2, and venous shear force is 0.5-4.0 dyne / cm2 [32].
Therefore, tumor cells need to adapt rapidly from static growth to fluid shear stress. This is a condition that static culture cannot handle. Until a few years ago, microdisks only supported 2D environments. Recently, 3D was introduced to support 3D aggregates. Finally, microfluidics have enabled the design and development of selforganized organ-like cell aggregates derived from the pluripotent stem cells organoids, opening up a whole new level of biomimetics. Typical examples are the blood-brain barrier, 3D neural network, kidney, liver, or intact intestinal epithelium, or glioma, breast cancer, or sarcoma model when it comes to cancerous tissue [30]. This technique has the ability to add multiple cell lines on the same chip. It is possible to mimic the interactions between tumors and endothelial cells that are the basis of the metastatic process, including, for example, angiogenesis, intravascular invasion, and colonization of cancer cells. Similarly, microfluidics has been thoroughly studied to better reproduce the interactions between cancer cells and immune cells, with the ultimate goal of expanding knowledge of cancer immunotherapy. Finally, the formation of 3D spheroids has been combined using hanging drops on a microfluidic platform for drug testing or chemical reaction assays. The next big challenge is to fully validate these models before implementing them in the pharmaceutical industry’s drug development pipeline and ultimately in personalized medicine applications.
Conclusion
Three-dimensional models have the potential to identify key molecular signaling pathways and establish a robust preclinical platform for assessing the clinical efficacy of new drugs that inhibit the development and progression of cancer.
Acknowledgement
Author would like to acknowledge Kassab Institute of Orthopedic for support.
Conflict of Interest
There are no conflict of interest.
References
- Mohseny AB, Szuhai K, Romeo S, Buddingh EP, Briaire-de Bruijn I, et al. (2009) Osteosarcoma originates from mesenchymal stem cells in consequence of aneuploidization and genomic loss of Cdkn2. J Pathol 219: 294-305.
- Lye KL, Nordin N, Vidyadaran S, Thilakavathy K (2016) Mesenchymal stem cells: from stem cells to sarcomas. Cell Biol Int 40: 610-618.
- Xiao W, Mohseny AB, Hogendoorn PC, Cleton-Jansen AM (2013) Mesenchymal stem cell transformation and sarcoma genesis. Clin Sarcoma Res 3:10.
- Cortini M, Avnet S, Baldini N (2017) Mesenchymal stroma: role in osteosarcoma progression. Cancer Lett 40: 90-99.
- Lemma S, Sboarina M, Porporato PE, Zini N, Sonveaux P, et al. (2016) Energy metabolism in osteoclast formation and activity. Int J Biochem Cell Biol 79:168-180.
- Lemma S, Di Pompo G, Porporato PE, Sboarina M, Russell S, et al. (2017) MDA-MB-231 breast cancer cells fuel osteoclast metabolism and activity: a new rationale for the pathogenesis of osteolytic bone metastases. Biochim Biophys Acta Mol Basis Dis 1863: 3254-3264.
- Sousa S, Clezardin P (2018) Bone-targeted therapies in cancer-induced bone disease. Calcif Tissue Int 102: 227-250.
- Costa-Rodrigues J, Fernandes A, Fernandes MH (2011) Reciprocal osteoblastic and osteoclastic modulation in co-cultured MG63 osteosarcoma cells and human osteoclast precursors. J Cell Biochem 112: 3704-3713.
- Salerno M, Avnet S, Alberghini M, Giunti A, Baldini N (2008) Histogenetic characterization of giant cell tumor of bone. Clin Orthop Relat Res 466:2081-2091.
- Alfranca A, Martinez-Cruzado L, Tornin J, Abarrategi A, Amaral T, et al. (2015) Bone microenvironment signals in osteosarcoma development. Cell Mol Life Sci 72: 3097-3113.
- Fitzgerald KA, Malhotra M, Curtin CM, O’Brien FJ, O’Driscoll CM (2015) Life in 3D is never flat: 3D models to optimise drug delivery. J Control Release 215: 39-54.
- Kinney MA, Hookway TA, Wang Y, McDevitt TC (2014) Engineering three-dimensional stem cell morphogenesis for the development of tissue models and scalable regenerative therapeutics. Ann Biomed Eng 42: 352-367.
- Sutherland RM, McCredie JA, Inch WR (1971) Growth of multicell spheroids in tissue culture as a model of nodular carcinomas. J Natl Cancer Inst 46: 113-120.
- Kelm JM, Timmins NE, Brown CJ, Fussenegger M, Nielsen LK (2003) Method for generation of homogeneous multicellular tumor spheroids applicable to a wide variety of cell types. Biotechnol Bioeng 83:173-180.
- Santo VE, Estrada MF, Rebelo SP, Abreu S, Silva I, et al. (2016) Adaptable stirred-tank culture strategies for large scale production of multicellular spheroid-based tumor cell models. J Biotechnol 221: 118-129.
- Breslin S, O’Driscoll L (2013) Three-dimensional cell culture: the missing link in drug discovery. Drug Discov Today 18: 240-249.
- Ishiguro T, Ohata H, Sato A, Yamawaki K, Enomoto T, et al. (2017) Tumor-derived spheroids: relevance to cancer stem cells and clinical applications. Cancer Sci 108: 283-289.
- Sutherland RM, McCredie JA, Inch WR (1971) Growth of multicell spheroids in tissue culture as a model of nodular carcinomas. J Natl Cancer Inst 46: 113-120.
- Ahmed EM (2015) Hydrogel: preparation, characterization, and applications: a review. J Adv Res 6: 105-121.
- Peck Y, Wang DA (2013) Three-dimensionally engineered biomimetic tissue models for in vitro drug evaluation: delivery, efficacy and toxicity. Expert Opin Drug Deliv 10: 369-383.
- Li Y, Kumacheva E (2018) Hydrogel microenvironments for cancer spheroid growth and drug screening. Sci Adv 4: eaas8998.
- Cortini M, Avnet S, Baldini N (2017) Mesenchymal stroma: role in osteosarcoma progression. Cancer Lett 405: 90-99.
- Avnet S, Di Pompo G, Lemma S, Baldini N (2019) Cause and effect of microenvironmental acidosis on bone metastases. Cancer Metastasis Rev 38: 133-147.
- Yoneda T, Hiasa M, Nagata Y, Okui T, White F (2015) Contribution of acidic extracellular microenvironment of cancer-colonized bone to bone pain. Biochim Biophys Acta 1848: 2677-2684.
- Di Pompo G, Lemma S, Canti L, Rucci N, Ponzetti M, et al. (2017) Intratumoral acidosis fosters cancer-induced bone pain through the activation of the mesenchymal tumor-associated stroma in bone metastasis from breast carcinoma. Oncotarget 8: 54478-54496.
- Keogh MB, O’Brien FJ, Daly JS (2010) Substrate stiffness and contractile behaviour modulate the functional maturation of osteoblasts on a collagen-GAG scaffold. Acta Biomater 6: 4305-4313.
- Carletti E, Motta A, Migliaresi C (2011) Scaffolds for tissue engineering and 3D cell culture. Methods Mol Biol 695: 17-39.
- Thakuri PS, Liu C, Luker GD, Tavana H (2018) Biomaterials-based approaches to tumor spheroid and organoid modeling. Adv Healthc Mater 7: e1700980.
- Huh D, Hamilton GA, Ingber DE (2011) From 3D cell culture to organs-on-chips. Trends Cell Biol 21: 745-754.
- Sontheimer-Phelps A, Hassell BA, Ingber DE (2019) Modelling cancer in microfluidic human organs-on-chips. Nat Rev Cancer 19: 65-81.
- Chung M, Ahn J, Son K, Kim S, Jeon NL (2017) Biomimetic Model of Tumor Microenvironment on Microfluidic Platform. Adv Healthc Mater 6: 1700196.
- McCarty OJ, Ku D, Sugimoto M, King MR, Cosemans JM, et al. (2016) Dimensional analysis and scaling relevant to flow models of thrombus formation: communication from the SSC of the ISTH. J Thromb Haemost 14: 619-622.
Indexed at, Google Scholar, Crossref
Indexed at, Google Scholar, Crossref
Indexed at, Google Scholar, Crossref
Indexed at, Google Scholar, Crossref
Indexed at, Google Scholar, Crossref
Indexed at, Google Scholar, Crossref
Indexed at, Google Scholar, Crossref
Indexed at, Google Scholar, Crossref
Indexed at, Google Scholar, Crossref
Indexed at, Google Scholar, Crossref
Indexed at, Google Scholar, Crossref
Indexed at, Google Scholar, Crossref
Indexed at, Google Scholar, Crossref
Indexed at, Google Scholar, Crossref
Indexed at, Google Scholar, Crossref
Indexed at, Google Scholar, Crossref
Indexed at, Google Scholar, Crossref
Indexed at, Google Scholar, Crossref
Indexed at, Google Scholar, Crossref
Indexed at, Google Scholar, Crossref
Indexed at, Google Scholar, Crossref
Indexed at, Google Scholar, Crossref
Indexed at, Google Scholar, Crossref
Indexed at, Google Scholar, Crossref
Indexed at, Google Scholar, Crossref
Indexed at, Google Scholar Crossref
Indexed at, Google Scholar, Crossref
Indexed at, Google Scholar, Crossref
Indexed at, Google Scholar, Crossref
Citation: Jlalia Z (2022) Primary Bone Tumors and its Advancement into 3D. J Orthop Oncol 8: 175. DOI: 10.4172/2472-016X.1000175
Copyright: © 2022 Jlalia Z. 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.
Share This Article
Recommended Journals
Open Access Journals
Article Tools
Article Usage
- Total views: 1151
- [From(publication date): 0-2022 - Aug 17, 2024]
- Breakdown by view type
- HTML page views: 963
- PDF downloads: 188