Pharmacological and functional properties of TRPM8 channels in prostate tumor cells
| Autor: | Cruz Morenilla-Palao, Carlos Belmonte, María Ll. Valero, Félix Viana |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Male
medicine.medical_specialty Cancer cells Thermosensitivity Pyridines Physiology Proliferation Clinical Biochemistry Glycine BCTC TRPM Cation Channels Pyrimidinones DU145 Arginine Endoplasmic Reticulum Cell Line chemistry.chemical_compound Transient receptor potential channel PC3 Calcium influx Cell Line Tumor Physiology (medical) Internal medicine TRP channel LNCaP medicine TRPM8 Humans Clotrimazole Ion channel Endoplasmic reticulum Cell Membrane Prostate Icilin Prostatic Neoplasms Cell biology Cold Temperature Menthol Endocrinology chemistry Transient receptor potential Pyrazines Cancer cell Calcium |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| ISSN: | 1432-2013 0031-6768 2007-6185 |
| DOI: | 10.1007/s00424-010-0895-0 |
| Popis: | 16 p., 7 figures, 1 table and references. Prostate cancer (PC) is a major health problem in adult males. TRPM8, a cationic TRP channel activated by cooling and menthol is upregulated in PC. However, the precise role of TRPM8 in PC is still unclear. Some studies hypothesized that TRPM8-mediated transmembrane Ca 2+ fluxes play a key role in cellular proliferation of PC cells. In contrast, other findings suggest that high TRPM8 levels may reduce the metastatic potential of PC cells. A detailed understanding of the response of TRPM8 channels to pharmacological modulators of their activity is relevant when considering potential therapies, targeting this ion channel to treat PC. We characterized the pharmacological and functional properties of native TRPM8 channels in four human prostate cell lines, PNT1A, LNCaP, DU145, and PC3, commonly used as experimental models of PC. PNT1A is a non-tumoral prostate cell line while the other three correspond to different stages of PC. Here, we show that cold- and agonist-evoked [Ca 2+] i responses in PC cells are much less sensitive to well-characterized agonists (menthol and icilin) and antagonists (BCTC, clotrimazole, and DD01050) of TRPM8 channels, compared to TRPM8 channels in other tissues, suggesting a different molecular composition and/or spatial organization. In addition, the forced overexpression of human TRPM8 facilitated the trafficking of TRPM8 channels residing in the endoplasmic reticulum to the plasma membrane, leading to a marked potentiation in the efficacy of the different blockers. These results predict that blockers of canonical TRPM8 channels may be less effective in halting proliferation of PC cells than expected. This work was supported by funds from the Spanish MICIIN: projects BFU2007-61855 to F.V and BFU2008-04425 and CONSOLIDER-INGENIO 2010 CSD2007-00023 to C.B. M.V. was the recipient of a predoctoral fellowship of the Spanish Government and C.M. holds a postdoctoral fellowship from FIS. |
| Databáze: | OpenAIRE |
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