TRPV1 in malignant progression of cancer
Breast cancer is a malignant disease that represents an important burden to public health. The description of new molecular markers can be important for diagnosis, classification and treatment. TRPV1 (vanilloid transitory receptor potential type 1) is expressed in different neoplastic tissues and its expression is associated with the regulation of tumor growth, cancer pain and malignant progression. It is known that in malignant progression regional metastasis is followed by distant metastasis, with a worse prognosis; however, the mechanisms underlying lymph node metastasis are poorly understood. We recently report that, intracellular distribution of TRPV1 in invasive breast carcinomas can be considered as prognostic biomarker of malignant progression. In this context, endogenous and exogenous agonists could modify TRPV1 endocytosis and exocytosis trafficking related to cancer malignancy and cancer pain. It is possible that, the changes in the subcellular distribution of TRPV1 is able to induce paracrine communication between cancer cell and surrounding stromal cell through changes in the secretome. Thus, micro vesicles profiles and the set of substances secreted bidirectionally, supports the incipient aggressive communication system between the tumor and pre-metastatic niches. In fact, lipids and steroids metabolites have been recognized as important modulators of transient receptor potential (TRP) channels. Specifically, TRPV1 is a polimodal receptor activated by a wide range of stimuli including allosteric modulation through binding of lipids and sterols able to bind spontaneously to the same hydrophobic pocket near the S5 helix. However, neoplastic mechanisms underlying TRPV1-dependent activation and tachyphylaxis is not properly understood. Thus, TRPV1-mediated cancer malignancy and cancer pain could become a pharmacological target to personalized coadjuvant therapies able to improve survival and quality of life in breast cancer patients.
