Pericytes in Tumor Vessels

Pericytes are specialized mural cells that closely interact with endothelial cells to regulate vascular development, stability, and homeostasis through signaling pathways including PDGF-B/PDGFR-β, TGF-β, Angiopoietin-1/Tie2, and N-cadherin. In cancer, they display remarkable phenotypic and functional plasticity, becoming key regulators of tumor angiogenesis and the tumor microenvironment. Disrupted pericyte-endothelial interactions contribute to the formation of abnormal, highly permeable blood vessels, promoting hypoxia, tumor progression, immune evasion, and metastasis. Beyond their vascular role, pericytes actively communicate with tumor-associated macrophages, cancer-associated fibroblasts, and extracellular matrix components, thereby influencing epithelial-to-mesenchymal transition, pre-metastatic niche formation, and therapeutic resistance. Increasing evidence also suggests that pericytes undergo phenotypic transitions that further support tumor progression. Conversely, restoring pericyte function and promoting vessel normalization have emerged as promising strategies to improve vascular integrity, tissue oxygenation, drug delivery, and the efficacy of anti-angiogenic therapies and immunotherapy. Preclinical and early clinical studies indicate that targeting pathways regulating pericyte recruitment and function, particularly in combination with endothelial-directed therapies, may produce synergistic anti-tumor effects. This review highlights the multifaceted roles of pericytes in tumor vascular remodeling, immune regulation, metastasis, and their potential as therapeutic targets in cancer.