Intracellular aggregated TRPV1 is associated with lower survival in breast cancer patients

Abstract

BackgroundBreast cancer is a malignant disease that represents an important public health burden. The description of new molecular markers can be important to diagnosis, classification, and treatment. Transient receptor potential vanilloid 1 (TRPV1) polymodal channel is expressed in different neoplastic tissues and cell lines of breast cancer and associated with the regulation of tumor growth, tumor neurogenesis, cancer pain, and malignant progression of cancer. In primary and metastatic breast cancer tumors, TRPV1 is expressed during neoplastic transformation, invasive behavior, and resistance to cytotoxic therapy.ObjectiveThe objective of this study was to describe the subcellular distribution of TRPV1 in invasive breast carcinomas and its association with survival.MethodsIn 33 cases of invasive breast carcinomas, we identified immunohistochemical and immunofluorescent expression patterns of TRPV1 compared to healthy breast tissue. We characterized the expression of TRPV1 induced by estrogens in breast cancer cell lines MCF-7 and MDA to establish a model of the TRPV1–estrogen relationship regarding the malignant potential. We examined the association of TRPV1 patterns with patients’ survival with the Kaplan–Meyer model, using the log-rank test at 5 years of follow-up. The relation of TRPV1 expression patterns to the St. Gallen breast cancer subtypes was also tested.ResultsBased on immunohistochemical expression pattern of TRPV1, we distinguished two main categories of breast cancer tissue, a “classical category” that exhibited diffuse expression of the channel and a “non-classical category” that expressed the channel in aggregates at the ER/Golgi and/or surrounding these structures. The classical pattern of TRPV1 was associated with a higher survival rate. In breast cancer cell lines, increasing doses of estrogens induced increased TRPV1 expression with nonclassical patterns at higher doses via a mechanism dependent on ER α.ConclusionThe expression and distribution of TRPV1 in invasive breast carcinomas may be considered as a biomarker for prognosis of the disease and a probable therapeutic target.

TRPV1 acts as a Tumor Suppressor and is associated with Immune Cell Infiltration in Clear Cell Renal Cell Carcinoma: evidence from integrated analysis

“…Furthermore, the study by Miao et al found highly expressed TRPV1 coupled with better DFS, which was consistent with our finding. However, another article launched by Lozano et al considered that the effect of TRPV1 on cancer survival was not completely dependent on expression quantity but on the distribution pattern [29]. Those researchers defined two patterns: one is the "classical category" that exhibited diffuse expression in whole cells, and the other is the "nonclassical category" that is expressed in aggregates at the ER/Golgi structures.…”

Transient Receptor Potential (TRP) Channels in Head-and-Neck Squamous Cell Carcinomas: Diagnostic, Prognostic, and Therapeutic Potentials

“…Other TRP channels seem to have prognostic value. For example, TRPV2 overexpression predicts adverse outcome in patients with esophageal SCC [ 103 ], and TRPM7-positive NPC patients also have worse prognosis than those with TRPM7-negative cancer [ 126 ]. As of today, it is unclear if altered TRP channel expression is the cause or consequence of the disease.…”

“…Interestingly, the reverse seems to be true for kidney cancer where TRPV1 is strongly expressed in normal renal tubules with much reduced (or absent) expression in renal cell carcinoma [ 102 ]. Moreover, TRPV1 is a potential negative prognostic marker in breast cancer where TRPV1 expression in the endoplasmic reticulum and Golgi apparatus (and/or the surrounding of these structures) heralds poor prognosis [ 103 ]. It remains to be determined if this observation also holds true for HNSCC ( Table 1 ).…”

TRPV1 Antagonist DWP05195 Induces ER Stress-Dependent Apoptosis through the ROS-p38-CHOP Pathway in Human Ovarian Cancer Cells

“…Reportedly, TRPV1 is expressed in various human cancer tissues [ 21 , 22 , 23 , 24 , 25 , 26 ], with TRPV1 expression found to be associated with lower survival in invasive breast carcinoma [ 27 ]. In melanoma tissues, decreased TRPV1 expression has been observed when compared to normal melanocytes, and TRPV1 overexpression inhibits melanoma growth via Ca 2+ signaling.…”