Angiocrine and pericrine signaling: how endothelial cells and pericytes drive cancer progression and therapy resistance

The emergence of treatment resistance and metastasis are significant challenges that need to be addressed to improve cancer patient outcomes. Greater insight into the mechanisms regulating these processes is needed to identify novel targets for the development of effective treatments. The importance of blood vessel interactions, including endothelial angiocrine and pericyte pericrine signals, with surrounding tissues, has been well established in regulating several normal physiological functions, including angiogenesis, metabolism, wound healing, and development. They have also been implicated in the mechanisms of cancer growth, metastatic dissemination, regulation of the immune microenvironment, and therapeutic resistance. This review provides an overview of the angiocrine and pericrine processes that regulate cancer, the tumor microenvironment, and therapy responses. It highlights that endothelial cells and pericytes are not only important in maintaining blood vessel structure in cancer but that their signaling roles are a pivotal regulatory element harnessed by tumors, some of which could be targeted for alternative cancer treatment strategies. Here, we summarize current research targeting angiocrine and pericrine signaling in cancer and propose new approaches for thorough exploration of these networks to further disentangle the intricate mechanisms at play.