Tumor-Associated Pericytes: Tumorigenicity and Targeting for Cancer Therapy

Abstract: Pericytes, also known as mural cells, are cells embedded between endothelial cells and the basement membrane of capillaries, where they orchestrate the morphological and functional homeostasis of blood vessels. Within the tumor microenvironment, pericytes interact closely with various cellular components, including tumor cells, stromal cells, and immune cells. Through these dynamic interactions, pericytes are activated and subsequently transform into tumor-associated pericytes (TPCs). The origin of TPCs varies depending on the tissue and tumor type, contributing to their phenotypic and functional heterogeneity. TPCs play pivotal roles in facilitating tumor progression, metastasis, immune evasion, and therapeutic resistance by promoting angiogenesis, engaging in reciprocal interactions with tumor cells, remodeling the extracellular matrix, and fostering an immunosuppressive microenvironment. This review synthesizes the latest significant advancements in targeted therapies against TPCs. It underscores the challenges inherent in developing effective anti-TPC therapies, which include the heterogeneity and pluripotency of TPCs, the absence of specific markers for precise TPC targeting, and the limited understanding of how current anti-tumor therapies affect TPCs and vice versa. This review furnishes a comprehensive understanding of the origins, markers, and functions of TPCs, and their interplays within the tumor microenvironment, providing prospective strategies for more effective anti-tumor therapy.