Carcinomas in general are composed of two interdependent components: the neoplastic epithelial cells and the supporting tumour stroma, which plays decisive roles in pivotal processes such as tumour cells proliferation, invasion, tumor vascularization and resistance to chemotherapy agents via the secretion of growth factors and cytokines.

A rise in intracellular Ca2+ concentration ([Ca2+]i) due to Ca2+ influx through the membrane Ca2+ channels is the main mechanism inducing exocytosis. In this context, we have recently shown that TRPA1 (Transient receptor Potential Ankyrin 1), was exclusively expressed in human prostate cancer (PCa) stromal cells (PrCSC). We hypothesised thus that TRPA1 channel is a key mediator in epithelia-stromal interactions, modulates the growth factors secretion, actively participates toin prostate carcinogenesis and therapeutic escape.

In the present work, by using primary cultured PrCSC derived from human PCa patients, we studied the role of TRPA1 channel in the physiology of prostate cancer stromal cells, in the expression and secretion of Hepatocyte Growth Factor (HGF). We further studied the modulation of the expression and functionality of the TRPA1 channel within epithelia-stromal crosstalk and the involvment of the channel in the resistance of the PCa cells to apoptosis induced by chemotherapeutics agents. The present data suggest that the stromal TRPA1 channel an actor of the prostate tumor microenvironment. Targeting TRPA1 channel could constitute a valuable tool in tumor microenvironment to disrupt epithelial-stromal interactions in human PCa. Indeed, in combination with chemotherapeutic agents, TRPA1 inhibition could decrease growth factors secretion by PrCSC cells and promote apoptosis induced by chemotherapeutic agents.