Role of mechanosensitive TRP channels in abnormal vasculature of tumors

Abstract

Solid tumors necessitate vascularization for metabolic support and metastasis, relying on the process of angiogenesis to form new blood vessels. However, the constant stimulation of endothelial cells from pro-angiogenic soluble factors and mechanical forces creates a tumor vasculature that is structurally and functionally abnormal. Most anti-angiogenic therapies have focused on targeting VEGF signaling to pursue the tumor vasculature. However, these anti-VEGF therapies have been met with limited success in clinical trials. Hence, recent studies have started to investigate the role of mechanical signaling in tumor angiogenesis as it occurs in a mechanically dynamic environment. This chapter focuses on mechanosensitive ion channels that belong to the transient receptor potential (TRP) superfamily, with special emphasis on the role of TRPV4 in the endothelium, as well as deregulation of TRPV4 signaling within the tumor endothelium, and its potential as a target for normalization of tumor vasculature to improve cancer therapy.