Transient Receptor Potential Melastatin-subfamily Member 7 Research Articles

Aberrantly Over-Expressed TRPM8 Channels in Pancreatic Adenocarcinoma: Correlation with Tumor Size/Stage and Requirement for Cancer Cells Invasion.

The transient receptor potential melastatin-subfamily member 8 (TRPM8) channels control Ca2+ homeostasis. Recent studies indicate that TRPM8 channels are aberrantly expressed and required for cellular proliferation in pancreatic adenocarcinoma. However, the functional significance of TRPM8 in pancreatic tissues is mostly unknown. The objectives of this study are to examine the expression of TRPM8 in various histopathological types of pancreatic tissues, determine its clinical significance in pancreatic adenocarcinoma, and investigate its functional role in cancer cells invasion. We present evidence that, in normal pancreatic tissues, anti-TRPM8 immunoreactivity is detected in the centroacinar cells and the islet endocrine cells. In pre-malignant pancreatic tissues and malignant neoplasms, TRPM8 is aberrantly expressed to variable extents. In the majority of pancreatic adenocarcinoma, TRPM8 is expressed at moderate or high levels, and anti-TRPM8 immunoreactivity positively correlates with the primary tumor size and stage. In the pancreatic adenocarcinoma cell lines that express relatively high levels of TRPM8, short hairpin RNA-mediated interference of TRPM8 expression impaired their ability of invasion. These data suggest that aberrantly expressed TRPM8 channels play contributory roles in pancreatic tumor growth and metastasis, and support exploration of TRPM8 as a biomarker and target of pancreatic adenocarcinoma.

Functional Expression of TRPM8 and TRPA1 Channels in Rat Odontoblasts

Odontoblasts produce dentin during development, throughout life, and in response to pathological conditions by sensing stimulation of exposed dentin. The functional properties and localization patterns of transient receptor potential (TRP) melastatin subfamily member 8 (TRPM8) and ankyrin subfamily member 1 (TRPA1) channels in odontoblasts remain to be clarified. We investigated the localization and the pharmacological, biophysical, and mechano-sensitive properties of TRPM8 and TRPA1 channels in rat odontoblasts. Menthol and icilin increased the intracellular free Ca2+ concentration ([Ca2+]i). Icilin-, WS3-, or WS12-induced [Ca2+]i increases were inhibited by capsazepine or 5-benzyloxytriptamine. The increase in [Ca2+]i elicited by allyl isothiocyanate (AITC) was inhibited by HC030031. WS12 and AITC exerted a desensitizing effect on [Ca2+]i increase. Low-temperature stimuli elicited [Ca2+]i increases that are sensitive to both 5-benzyloxytriptamine and HC030031. Hypotonic stimulation-induced membrane stretch increased [Ca2+]i; HC030031 but not 5-benzyloxytriptamine inhibited the effect. The results suggest that TRPM8 channels in rat odontoblasts play a role in detecting low-temperature stimulation of the dentin surface and that TRPA1 channels are involved in sensing membrane stretching and low-temperature stimulation. The results also indicate that odontoblasts act as mechanical and thermal receptor cells, detecting the stimulation of exposed dentin to drive multiple cellular functions, such as sensory transduction.

Cooling skin cancer: menthol inhibits melanoma growth. Focus on “TRPM8 activation suppresses cellular viability in human melanoma”

yamamura and colleagues ([17][1]) report that melanoma cells express transient receptor potential melastatin subfamily member 8 (TRPM8) receptors and that their activation suppresses melanoma viability. This effect is mediated by menthol, and the mechanism of action involves the influx of