Open AccessBlockade of TRPM8 activity reduces the invasion potential of oral squamous carcinoma cell lines
Author(s) -
Yoshihiko Okamoto,
Tsuyako Ohkubo,
Tetsuro Ikebe,
Jun Yamazaki
Publication year - 2012
Publication title -
international journal of oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.405
H-Index - 122
ISSN - 1019-6439
DOI - 10.3892/ijo.2012.1340
Subject(s) - trpm8 , transient receptor potential channel , biology , intracellular , cancer research , cancer , menthol , squamous carcinoma , pharmacology , microbiology and biotechnology , chemistry , medicine , receptor , biochemistry , carcinoma , trpv1 , organic chemistry
Several members of the transient receptor potential (TRP)-channel familyare expressed in cancer cells. One, cold/menthol-sensitive TRPM8, is reportedlyan important player in carcinogenesis in human prostate cancer, although its involvementin oral squamous cell carcinoma (SCC) remains unclear. The present immunohistochemistryand RT-PCR results revealed intense TRPM8 expression in two SCC cell lines, HSC3and HSC4, derived from the human tongue. Menthol, icilin, and a more specificTRPM8 agonist (WS-12) induced non-specific cation currents, with Ca2+ permeabilitybeing greater than that of Na+ or K+. The novel TRPM8 antagonist RQ-00203078 (RQ)profoundly reduced such agonist-induced cation currents. Intracellular Ca2+ imagingrevealed that menthol induced both intracellular Ca2+ release and store-operatedCa2+ entry, with RQ inhibiting each effect. To assess the possible pathophysiologicalrole of TRPM8 in oral SCC, we performed motility and invasion assays, and gelatinzymography. Menthol augmented the migration and invasion abilities of both HSC3and HSC4 cells by potentiating MMP-9 activity. RQ suppressed all of these effects.These results may aid understanding of the pathophysiological implications ofTRPM8 channels in the oral SCC cells, support TRP proteins as valuable targetsfor pharmaceutical intervention, and inform the targeting of oral SCC in whichthe prognosis is poor.