Combined effects of pericytes in the tumor microenvironment

Abstract

Pericytes are multipotent perivascular cells whose involvement in vasculature development is well established. Evidences in the literature also suggest that pericytes display immune properties and that these cells may serve as an in vivo reservoir of stem cells, contributing to the regeneration of diverse tissues. Pericytes are also capable of tumor homing and are important cellular components of the tumor microenvironment (TME). In this review, we highlight the contribution of pericytes to some classical hallmarks of cancer, namely, tumor angiogenesis, growth, metastasis, and evasion of immune destruction, and discuss how collectively these hallmarks could be tackled by therapies targeting pericytes, providing a rationale for cancer drugs aiming at the TME.

Figure 1

Abnormal pericyte coverage of tumor vessels affects tumor development. PDGF-β signaling controls pericyte recruitment during angiogenesis. Hyperactivation of this pathway within TME may increase pericyte coverage, thereby improving vasculature stability and perfusion, which favors tumor growth. In contrast, low pericyte coverage compromises vessel structure integrity, which becomes leaky, facilitating tumor cell invasion/extravasion. Under such circumstances, tumor cells may also undergo EMT induced by hypoxia, as a consequence of lower perfusion in the tumor vasculature. Both situations enhance metastatic spread of tumor cells.

Figure 2

Interplay between pericytes and cancer stem cells. In brain cancer, the perivascular niche is critical to the maintenance of CSC pool. Perivascular cells promote self-renewal and impair differentiation of CSC. In turn, new pericytes may be generated by CSC, contributing to tumor angiogenesis and tumor scape from immune destruction. This reciprocal interaction between pericytes and CSC is highly beneficial to tumor development.