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Blockade of TRPM8 activity reduces the invasion potential of oral squamous carcinoma cell lines
- Source :
- International Journal of Oncology.
- Publication Year :
- 2012
- Publisher :
- Spandidos Publications, 2012.
-
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.
- Subjects :
- Cancer Research
Patch-Clamp Techniques
TRPM Cation Channels
Antineoplastic Agents
Pyrimidinones
Biology
Real-Time Polymerase Chain Reaction
Membrane Potentials
Transient receptor potential channel
chemistry.chemical_compound
Cell Movement
Cell Line, Tumor
TRPM8
Humans
Anilides
Neoplasm Invasiveness
Calcium Signaling
RNA, Messenger
Cell Proliferation
Oncogene
Reverse Transcriptase Polymerase Chain Reaction
Icilin
Cell cycle
Immunohistochemistry
Tongue Neoplasms
Squamous carcinoma
Menthol
stomatognathic diseases
Matrix Metalloproteinase 9
Oncology
chemistry
Cancer cell
Immunology
Carcinoma, Squamous Cell
Cancer research
Intracellular
Subjects
Details
- ISSN :
- 17912423 and 10196439
- Database :
- OpenAIRE
- Journal :
- International Journal of Oncology
- Accession number :
- edsair.doi.dedup.....bda8697327247f8ca34fc789f4090b9a