Neuropilin: Handyman and Power Broker in the Tumor Microenvironment

Abstract

Neuropilin-1 and neuropilin-2 form a small family of transmembrane receptors, which, due to the lack of a cytosolic protein kinase domain, act primarily as co-receptors for various ligands. Performing at the molecular level both the executive and organizing functions of a handyman as well as of a power broker, they are instrumental in controlling the signaling of various receptor tyrosine kinases, integrins, and other molecules involved in the regulation of physiological and pathological angiogenic processes. In this setting, the various neuropilin ligands and interaction partners on various cells of the tumor microenvironment, such as cancer cells, endothelial cells, cancer-associated fibroblasts, and immune cells, are surveyed. The suitability of various neuropilin-targeting substances and the intervention in neuropilin-mediated interactions is considered as a possible building block of tumor therapy.

Keywords: Cancer cell; Endothelial cell; Neuropilin interacting partners; Neuropilin ligands; Neuropilin signaling; Semaphorin; Tumor angiogenesis; Tumor microenvironment; Tumor stromal cell; Tumor-penetrating peptides; Vascular endothelial growth factor.