High Expression of Transient Receptor Potential Channels in Human Breast Cancer Epithelial Cells and Tissues: Correlation with Pathological Parameters

Abstract

Background: Transient Receptor Potential (TRP) channels are expressed in many solid tumors. However, their expression in breast cancer remains largely unknown. Here, we investigated the profile expression of 13 TRP channels in human breast ductal adenocarcinoma (hBDA) and performed a correlation between their overexpression and pathological parameters. Methods: The TRP channels expression was determined by RT-PCR in hBDA tissue, in human breast cancer epithelial (hBCE) primary culture and in MCF-7 cell line. The TRP protein level was evaluated by immunohistochemistry in hBDA tissue samples of 59 patients. Results: TRPC1, TRPC6, TRPM7, TRPM8, and TRPV6 channels were overexpressed in hBDA compared to the adjacent non-tumoral tissue. Most interestingly, TRPC1, TRPM7 and TRPM8 expression strongly correlated with proliferative parameters (SBR grade, Ki67 proliferation index, and tumor size), and TRPV6 was mainly overexpressed in the invasive breast cancer cells. Using laser capture microdissection, we found that TRPV6 expression was higher in invasive areas, compared to the corresponding non-invasive ones. Moreover, TRPV6 silencing inhibited MDA-MB-231 migration and invasion, and MCF-7 migration. Conclusion: TRP channels are aberrantly expressed in hBDA, hBCE primary cultures, and cell lines, and associated with pathological parameters. The high expression of TRP channels in tumors suggests the potential of these channels for diagnostic, prognosis and/or therapeutic approaches in human breast ductal adenocarcinoma.

Calcium Channel TRPV6 as a Potential Therapeutic Target in Estrogen Receptor–Negative Breast Cancer

“…This study also identified elevated mRNA levels (2-to 15-fold) of TRPV6 in 7 of 12 breast tumor samples (7). A very recent study has shown increased levels of TRPV6 in more invasive breast cancers (22). However, differences in TRPV6 have not been correlated with pathologic (e.g., histologic type) or molecular [e.g., estrogen receptor (ER) status or molecular subtypes] parameters or prognosis, as has recently been shown for regulators of store-operated calcium entry (9).…”

Transient receptor potential (TRP) channels, promising potential diagnostic and therapeutic tools for cancer

“…(22). Moreover, the activation of TRPC1 enhanced the proliferation of MCF-7 cells, a human breast cancer cell line with low metastatic potential, by stimulating phosphorylation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) and Ca 2+ entry (23).…”

“…TRPV6 silencing can inhibit MDA-MB-231 migration and invasion in addition to MCF-7 cell migration (22). Moreover, limited estrogen receptor (ER) signaling reportedly leads to lower levels of TRPV6 expression, and the antitumor effect of Tamoxifen may be related to the inhibition of TRPV6 expression (26).…”

Remodelling of Ca2+transport in cancer: how it contributes to cancer hallmarks?

“…Higher expression of TRPV2 in PCa cells or TRPM8 in squamous cell carcinoma correlated with the induction of MMP-2, MMP-9 and cathepsin B [73,75]. Using laser capture microdissection of breast tumour tissue, it was established that higher expression of TRPV6 channel tend to localize in the invasive areas, compared with the non-invasive ones, and TRPV6 silencing was able to inhibit migration and invasion of breast cancer cells [40]. However, with respect to TRPV1 channel diverging results have been reported, suggesting that its role in malignant motility and invasion may be cancer cell-specific.…”