Mechanisms of Pericyte-Mediated Cancer Metastasis

Emerging experimental evidence shows that perivascular cells (PCs), referred to as pericytes lying within the basement membrane (BM) and surrounding endothelial cells (ECs) of microvasculatures, play multifarious roles in cancer metastasis. In the tumor microenvironment (TME), PC detachment and ablation from tumor microvessels obliterate the vascular integrity and the protective barrier of the vessel wall, leading to increased permeability for cancer cell intravasation. PCs retain mesenchymal stem cell (MSC) features and commit to differentiation into other stromal cells, including the pericyte-fibroblast transition (PFT) for promoting cancer metastasis. Activated PCs produce a myriad of growth factors, cytokines, and chemokines, which promote invasiveness and dissemination of cancer cells by altering tumor angiogenic, inflammatory, and immune microenvironment. Owing to their high lineage and phenotypic plasticity, PCs significantly constitute to the pre-metastatic niche formation in distal organs. This review provides an updated overview and mechanistic insights into each of PC-mediated critical processes of the metastatic cascade.