Review of Pericytes in Tumor Biology

Abstract

Pericytes are contractile cells that surround the endothelium of capillaries and venules throughout the body. Pericytes were once thought to have a limited role in blood pressure control and angiogenesis. Today, knowledge about pericytes and other perivascular stem cells has vastly expanded. The understanding of the biologic significance of pericytes was most changed by the recognition of the perivascular identity of mesenchymal stem cells. The following review article will summarize the known functions and importance of pericytes in particular relevance to tumor biology. These roles include: (1) pericytes as the potential cell of origin for multiple soft tissue tumors; (2) the role of pericyte in regulating tumor cell vascular invasion; and 3) angiotropism or 'pericytic mimicry' as a mechanism of malignant tumor spread. Although not discussed, the role of pericytes in pathophysiology far exceeds the realms of tumor biology, including cardiovascular atherosclerotic disease, chronic kidney disease, fibrotic repair processes, and fibroproliferative diseases. In summary, the known roles of pericytes in tumor formation, growth, and invasion have greatly expanded. These include pericytic differentiation in soft tissue tumors, regulation of vascular invasion in solid tumors, and extravascular migratory migration of common malignancies.

Pericytes in Glioblastomas: Multifaceted Role Within Tumor Microenvironments and Potential for Therapeutic Interventions

“…Brain metastatic lung and melanoma cells that extravasate through capillaries were shown to survive and proliferate for long periods of time only when in contact with the abluminal endothelial cells of capillaries in a pericyte-like position. This mechanism where tumor cells position themselves similar to pericytes when in contact with the abluminal endothelial cells has been extensively studied in melanomas and is termed as pericyte mimicry or angiotropism (Bentolila et al 2016;Lugassy et al 2014;Scott et al 2015). Pericyte mimicry not only allows for the survival and proliferation of tumor cells but has also been reported to be exploited by tumor cells for extravascular migratory metastasis.…”

“…This mechanism allows tumor cells to spread to local and distant sites by avoiding vascular invasion. GBM cells have been well documented in in vivo and in vitro studies to invade surrounding normal brain parenchyma along abluminal side of capillaries through the mechanism of pericyte mimicry (Scott et al 2015).…”

“…Behling et al and Sattiraju et al show the feasibility of targeting vascular and perivascular components within the NVU using short-ranged, targeted molecular irradiation to either enhance vascular perfusion or BBB permeability, to better deliver systemic drugs to GBMs and to reduce radio-resistance conferred by perivascular cells within GBM microenvironment. But, as evidenced in previous studies where pericyte ablation caused enhanced invasion and metastasis, further long-term evaluations to assess tumor resistance and remission in abovementioned strategies are necessary (Bentolila et al 2016;Lugassy et al 2014;Scott et al 2015). Xiong et al reported an alternative strategy of enhancing BBB permeability by remotely activating intracranially implanted genetically engineered MSCs using high-frequency focused ultrasound (HIFU) to secrete TNF-α.…”

Inhibition of Lysyl Oxidases Impairs Migration and Angiogenic Properties of Tumor-Associated Pericytes

“…One important, albeit less studied, cellular component of the TME is the pericyte population [ 6 ]. Pericytes are present along the microvessel walls where they are important for vasculature remodeling, maturation and stabilization, regulation of blood flow, and blood vessel permeability.…”

Caracterização do índice de cobertura por pericitos em neoplasias mamárias caninas e seu papel como fator prognóstico

“…Gerhardt & Betsholtz (2003) indicaram que a expressão α-SMA ocorria apenas em células murais maduras e tal dado foi confirmado por Wang et al (2006) que provaram que pericitos expressavam proteínas anti-α-SMA. Recentemente, Natarajan et al (2022) demonstraram que grande parte dos vasos sanguíneos intratumorais em cânceres pancreáticos expressam o α-SMA, fenômeno este induzido pelas células cancerosas.A caracterização da microvasculatura e o papel dos pericitos ainda é fonte de estudos(SCOTT et al, 2015) e este interesse se dá principalmente nos resultados muitas vezes frustrantes dos tratamentos oncológicos utilizando-se drogas antiangiogênicas(JIANG et al, 2018;MENG et al, 2015). Este tipo de terapia lança mão de moléculas que inibem a via de sinalização do VEGF, destruindo a vasculatura e, em última instância, matando as células tumorais (KIM, 2019) Franco et al (2011).…”