ISSN: 2161-0681

Journal of Clinical & Experimental Pathology
Open Access

Our Group organises 3000+ Global Conferenceseries Events every year across USA, Europe & Asia with support from 1000 more scientific Societies and Publishes 700+ Open Access Journals which contains over 50000 eminent personalities, reputed scientists as editorial board members.

Open Access Journals gaining more Readers and Citations
700 Journals and 15,000,000 Readers Each Journal is getting 25,000+ Readers

This Readership is 10 times more when compared to other Subscription Journals (Source: Google Analytics)
  • Perspective   
  • J Clin Exp Pathol, Vol 13(1)
  • DOI: 10.4172/2161-0681.23.13.429

Clinical Approach for Vessel Co-Option: From the Pathologist’s Perspective

José I. López1* and Aurelio Ariza2*
1Biomarkers in Cancer Unit, Biocruces-Bizkaia Health Research Institute, Barakaldo, Spain
2Department of Pathology, Autonomous University of Barcelona, Barcelona, Spain
*Corresponding Author(s): José I. López, Biomarkers in Cancer Unit, Biocruces-Bizkaia Health Research Institute, Barakaldo, Spain, Email: jilpath@gmail.com
Aurelio Ariza, Department of Pathology, Autonomous University of Barcelona, Barcelona, Spain, Email: aurelioariza152@gmail.com

Received: 07-Feb-2023 / Manuscript No. JCEP-23-88877 / Editor assigned: 09-Feb-2023 / PreQC No. JCEP-23-88877 / Reviewed: 23-Feb-2023 / QC No. JCEP-23-88877 / Revised: 07-Mar-2023 / Manuscript No. JCEP-23-88877 / Published Date: 24-Mar-2023 DOI: 10.4172/2161-0681.23.13.429

Description

Blood vessel formation is a key ingredient of both organogenesis and tissue repair, in which florid endothelial sprouting takes place in the distal parts of the vascular system. This biological process, whose main goal is increasing oxygen and nutrients supply to tissues, is called angiogenesis. Importantly, this microvascular development also fuels neoplastic growth. Together with tumor-infiltrating lymphocytes, macrophages, and cancer-associated fibroblasts, endothelia constitute a major component of the tumor microenvironment. The mechanisms by which tumor cells induce angiogenesis have been extensively analyzed [1].

Interestingly, researchers soon noticed that a significant percentage of primary tumors showed no histological evidence of angiogenesis. Since, contrary to expectations, these tumors did not develop hypoxia, it was concluded that they probably resorted to an alternative way of oxygen and nutrients supply. Pezzella reached this conclusion in 1997, when they noticed that 16% of aggressive stage I non-small-cell lung carcinomas in their series of 500 cases lacked features of vascular sprouting [2]. Further evidence accrued in the last decades has confirmed that these non-angiogenic neoplasms are more frequent than previously suspected and tend to display a more aggressive clinical course [3].

Vessel co-option, a term coined by Holash in 1999, refers to the hijacking of pre-existing vascular networks by neoplastic tissue [4]. This process, which could be considered as a sort of tumor parasitism, guarantees tumor blood supply in the absence of angiogenesis. On the other hand, this phenomenon provides alternative routes for tumor dissemination. Vessel co-option takes place everywhere, albeit it has been preferentially studied in primary and metastatic tumors involving organs such as the brain, lung, and liver [5].

Pathologists may detect vessel co-option traits under the microscope, but its identification is difficult and may be overlooked in a context of high diagnostic pressure. It is then of paramount importance to acquaint pathologists with the definitory histologic features of this interesting phenomenon. The issue matters because vessel co-option is responsible for extravascular migratory dissemination of neoplastic cells, a still poorly known mechanism of tumor spreading. Additionally, vessel co-option is associated with lack of therapeutic response to current anti-angiogenic drugs [5,6].

The morphological features of vessel co-option have been recently reviewed [3,7]. In the first place, specific organ histology must be kept in mind since wide organ-related variations in the microscopic findings of vessel co-option do occur. Thus, Virchow-Robin spaces in the brain, sinusoidal vessels in the liver, and per alveolar chicken-wire capillaries in the lung, among others, show different histological changes when co-opted.

At any rate, the main problem for pathologists is to distinguish immature (angiogenic) from mature (non-angiogenic) vessels in conventional hematoxylin-eosin-stained slides. Conventional vascular markers such as Factor VIII-related antigen, CD31, and CD34 are not useful for this purpose since endothelial cells in both immature and mature vessels are equally immunoreactive. Fortunately Smooth- Muscle Actin (SMA), which is expressed only in mature vessel pericytes (perivascular niche), is more helpful in this regard. Proliferation index (Ki67) may also be used to detect immature endothelial cells. In this setting, it is crucial to remember that angiogenesis and vessel co-option are not mutually exclusive and may coexist in the same tumor [5,8].

Due to the specific characteristics of brain tissue, its primary tumors and their metastases offer very useful scenarios for the study of vessel co-option. In normal conditions the central nervous system parenchyma lacks connective tissue. This absence favors the development of a diffuse front of tumor infiltration, which is facilitated by co-opting the Virchow-Robin spaces. The mechanism underlying this co-option relies on the intricate interaction of tumor cells, basal membranes, and pericytes.

In addition to the common presence of abundant vessel sprouting and vascular proliferation in high-grade gliomas, the use of Virchow- Robin spaces as a route of expansion is commonly seen in gliomas and brain metastases [9]. The endothelial sprouting so characteristic of angiogenesis does not take place in the absence of stromal induction, even in the presence of high levels of local vascular growth factors. To better detect co-opting vessel features within the Virchow-Robin spaces, pathologists should focus on the tumor edge of infiltration. If needed, specific immunohistochemical markers may be used to highlight this phenomenon.

Aside from the central nervous system, vessel co-option is a common feature of hepatocellular carcinomas and liver metastases, in which pre-existing sinusoidal vessels are hijacked [6,10], and of lung carcinomas, in which the perialveolar capillary network is occupied by tumor cells [11]. Melanoma is a typical co-opter by often permeating the virtual perivascular space of local vessels in the skin or the organs to which it metastasizes [12].

Although renal clear cell carcinoma is one of the paradigmatic examples of angiogenic neoplasm, vessel co-option also occurs in this tumor. Of interest, the high density of mature vessels detected in the renal tissue at the tumor edge suggests that a process of pre-co-option vessel remodeling is taking place [13]. These vessels initially keep their pericyte coverage intact, but when co-opted and overrun by the tumor expansible growth their pericyte population gradually diminishes until its total disappearance in the necrotic tumor center [13].

Vessel co-option acquired special clinical relevance with the addition of anti-angiogenic drugs to oncologic therapeutic protocols. Resistance to this therapy has been well documented in most nonangiogenic tumors [5,6,10]. Additionally, some studies have shown that the perivascular niche generated in vessel co-option may also act as a sanctuary for tumor cell dormancy and a facilitator of immune therapy resistance [14].

Alternative therapies aiming at the inhibition of vessel co-option include the following: (i) suppression of tumor cell motility by knocking down the expression of actin-related protein 2/3, (ii) blockade of cell adhesion receptors such as L1CAM and cell adhesion receptor β1 integrin, and (iii) simultaneous inhibition of VEGF and angiopoietin signaling [5]. At present, however, these and other promising therapeutic alternatives are still under investigation. The successful outcome of these efforts is highly dependent on a better understanding of the vessel co-option phenomenon from the pathologist’s perspective.

Funding

Not applicable.

Conflict of Interest

The authors declare no conflict of interest.

Contributions

J.I.L. and A.A. designed, wrote, and approved the manuscript.

References

Citation: López JI, Ariza A (2023) Clinical Approach for Vessel Co-Option: From the Pathologist’s Perspective. J Clin Exp Pathol. 13: 429. DOI: 10.4172/2161-0681.23.13.429

Copyright: © 2023 López JI, 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.

Top