TRPV Channels in Tumor Growth and Progression

Abstract

Transient receptor potential (TRP) channels affect several physiological and pathological processes. In particular, TRP channels have been recently involved in the triggering of enhanced proliferation, aberrant differentiation, and resistance to apoptotic cell death leading to the uncontrolled tumor invasion. About thirty TRPs have been identified to date, and are classified in seven different families: TRPC (Canonical), TRPV (Vanilloid), TRPM (Melastatin), TRPML (Mucolipin), TRPP (Polycystin), and TRPA (Ankyrin transmembrane protein) and TRPN (NomPC-like). Among these channel families, the TRPC, TRPM, and TRPV families have been mainly correlated with malignant growth and progression. The aim of this review is to summarize data reported so far on the expression and the functional role of TRPV channels during cancer growth and progression. TRPV channels have been found to regulate cancer cell proliferation, apoptosis, angiogenesis, migration and invasion during tumor progression, and depending on the stage of the cancer, up- and down-regulation of TRPV mRNA and protein expression have been reported. These changes may have cancer promoting effects by increasing the expression of constitutively active TRPV channels in the plasma membrane of cancer cells by enhancing Ca(2+)-dependent proliferative response; in addition, an altered expression of TRPV channels may also offer a survival advantage, such as resistance of cancer cells to apoptotic-induced cell death. However, recently, a role of TRPV gene mutations in cancer development, and a relationship between the expression of specific TRPV gene single nucleotide polymorphisms and increased cancer risk have been reported. We are only at the beginning, a more deep studies on the physiopathology role of TRPV channels are required to understand the functional activity of these channels in cancer, to assess which TRPV proteins are associated with the development and progression of cancer and to develop further knowledge of TRPV proteins as valuable diagnostic and/or prognostic markers, as well as targets for pharmaceutical intervention and targeting in cancer.

Upregulation of Transient Receptor Potential Vanilloid Type-1 Channel Activity and Ca2+Influx Dysfunction in Human Pterygial Cells

“…These TRPV1-mediated Ca 2þ transients and current response patterns correspond to those described in many studies using different cell types, including tumor cells. 26,27,38,40,[45][46][47][48] Because TRPV1 expression and activity are elevated in cancerous tissue, it is conceivable that TRPV1 and possible endogenous modulators may be a potential drug target to suppress proliferation not only in malignant tumors but also in benign hyperplastic tumors, such as pterygium (reviewed by Santoni et al 49 ).…”

“…4-6) suggests that reducing its activity may resolve tumor progression if increases in its activity precede or occur as a consequence of pterygial development. Dysregulated TRP channel activation contributes to also triggering, aberrant differentiation, and resistance to apoptotic cell death leading to uncontrolled tumor invasion (spread) (reviewed by Santoni et al 49 ). Transient Receptor Potential V1 (also classically known as a pain receptor [50][51][52] ) is a nociceptor that is a potential drug target for inhibiting cancer pain in bone metastases, pancreatic cancer, and most likely in other cancers (reviewed in Refs.…”

Resiniferatoxin induces death of bladder cancer cells associated with mitochondrial dysfunction and reduces tumor growth in a xenograft mouse model

“…Very few data are available on its use as chemotherapeutic agent. The anticancer activity of vanilloids such as capsaicin and dihydrocapsaicin can be mediated through both a direct pathway, independent of transient receptor potential vanilloid receptor 1 (TRPV1), the receptor for vanilloids, and an indirect pathway, through the interaction with TRPV1 and the subsequent intracellular calcium overload [10][11][12][13][14][15][16]. In regard to RTX, there are indications that mitochondria could be involved in the TRPV1-independent vanilloids-induced cell death.…”

Nanoheating without Artificial Nanoparticles

“…TRPV1, TRPV2 and TRPV6) in cancer growth has recently been reported [34,35]. Changes in TRPV1 expression occur during the development of human urothelial cancer [36].…”