RRC ID 43643
著者 Okamoto Y, Ohkubo T, Ikebe T, Yamazaki J.
タイトル Blockade of TRPM8 activity reduces the invasion potential of oral squamous carcinoma cell lines.
ジャーナル Int J Oncol
Abstract Several members of the transient receptor potential (TRP)-channel family are expressed in cancer cells. One, cold/menthol-sensitive TRPM8, is reportedly an important player in carcinogenesis in human prostate cancer, although its involvement in oral squamous cell carcinoma (SCC) remains unclear. The present immunohistochemistry and RT-PCR results revealed intense TRPM8 expression in two SCC cell lines, HSC3 and HSC4, derived from the human tongue. Menthol, icilin, and a more specific TRPM8 agonist (WS-12) induced non-specific cation currents, with Ca2+ permeability being greater than that of Na+ or K+. The novel TRPM8 antagonist RQ-00203078 (RQ) profoundly reduced such agonist-induced cation currents. Intracellular Ca2+ imaging revealed that menthol induced both intracellular Ca2+ release and store-operated Ca2+ entry, with RQ inhibiting each effect. To assess the possible pathophysiological role of TRPM8 in oral SCC, we performed motility and invasion assays, and gelatin zymography. Menthol augmented the migration and invasion abilities of both HSC3 and HSC4 cells by potentiating MMP-9 activity. RQ suppressed all of these effects. These results may aid understanding of the pathophysiological implications of TRPM8 channels in the oral SCC cells, support TRP proteins as valuable targets for pharmaceutical intervention, and inform the targeting of oral SCC in which the prognosis is poor.
巻・号 40(5)
ページ 1431-40
公開日 2012-5-1
DOI 10.3892/ijo.2012.1340
PMID 22267123
MeSH Anilides / pharmacology Antineoplastic Agents / pharmacology* Calcium Signaling / drug effects Carcinoma, Squamous Cell / genetics Carcinoma, Squamous Cell / metabolism* Carcinoma, Squamous Cell / pathology Cell Line, Tumor Cell Movement / drug effects* Cell Proliferation / drug effects Humans Immunohistochemistry Matrix Metalloproteinase 9 / metabolism Membrane Potentials Menthol / analogs & derivatives Menthol / pharmacology Neoplasm Invasiveness Patch-Clamp Techniques Pyrimidinones / pharmacology RNA, Messenger / metabolism Real-Time Polymerase Chain Reaction Reverse Transcriptase Polymerase Chain Reaction TRPM Cation Channels / antagonists & inhibitors* TRPM Cation Channels / genetics TRPM Cation Channels / metabolism Tongue Neoplasms / genetics Tongue Neoplasms / metabolism* Tongue Neoplasms / pathology
IF 3.899
引用数 46
WOS 分野 ONCOLOGY
リソース情報
ヒト・動物細胞 HSC-3(RCB1975) HSC-4(RCB1902)