Blockade of TRPM8 activity reduces the invasion potential of oral squamous carcinoma cell lines
Blockade of TRPM8 activity reduces the invasion potential of oral squamous carcinoma cell lines
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DOI：
10.3892/ijo.2012.1340
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发表时间：
2012-05-01
影响因子：
5.2
通讯作者：
Yamazaki, Jun
中科院分区：
文献类型：
--
作者：
Okamoto, Yoshihiko;Ohkubo, Tsuyako;Yamazaki, Jun
瞬时受体电位（TRP）通道家族的几个成员在癌细胞中表达。其中之一，冷/薄荷敏感的TRPM 8，据报道是人类前列腺癌致癌作用的重要参与者，尽管其在口腔鳞状细胞癌（SCC）中的参与尚不清楚。目前的免疫组织化学和RT-PCR结果显示，强烈的TRPM 8表达在两个SCC细胞系，HSC 3和HSC 4，来自人舌。甲氨蝶呤，icilin，和一个更具体的TRPM 8激动剂（WS-12）诱导非特异性阳离子电流，与Ca 2+渗透性大于Na+或K+。新型TRPM 8拮抗剂RQ-00203078（RQ）显著降低了这种激动剂诱导的阳离子电流。细胞内Ca 2+成像显示，薄荷醇诱导细胞内Ca 2+释放和钙库操作的Ca 2+进入，RQ抑制每种效果。为了评估TRPM 8在口腔SCC中可能的病理生理作用，我们进行了运动和侵袭试验以及明胶酶谱分析。Meng通过增强MMP-9活性增强HSC 3和HSC 4细胞的迁移和侵袭能力。RQ抑制了所有这些效应。这些结果可能有助于理解TRPM 8通道在口腔SCC细胞中的病理生理学意义，支持TRP蛋白作为药物干预的有价值的靶点，并为预后不良的口腔SCC的靶向提供信息。
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.