Portal de Periódicos da CAPES

Characterization of Functional Transient Receptor Potential Melastatin 8 Channels in Human Pancreatic Ductal Adenocarcinoma Cells

2014; Lippincott Williams & Wilkins; Volume: 43; Issue: 5 Linguagem: Inglês

10.1097/mpa.0000000000000106

1536-4828

Dana Cucu, Gabriela Chirițoiu, Ştefana M. Petrescu, Alexandru Babeș, Luciana Stănică, Dan G. Duda, Akira Horii, Simona Dima, Irinel Popescu,

Ion channel regulation and function

Recently, the transient receptor potential melastatin 8 (TRPM8) channel has emerged as a putative biomarker for pancreatic ductal adenocarcinoma (PDA). This study aimed to evaluate the expression of TRPM8 and its modulation by specific agonists and antagonists in PDA cells.We examined the protein expression of TRPM8 in 3 different PDA cell lines and compared it with a nontumoral epithelial cell line of human pancreatic origin using Western blotting and immunocytochemical analysis. To assess the function of TRPM8 channels, we measured the TRPM8 currents in whole-cell mode of the patch clamp technique. To explore the putative involvement of TRPM8 in cell migration, we investigated the motility of PDA cells using the scratch-wound assay.Pancreatic ductal adenocarcinoma cells express functional plasma membrane TRPM8 channels, which are responsive after exposure to agonists (menthol and icilin) and antagonists N-(3-aminopropyl)-2-{[(3-methylphenyl) methyl]oxy}-N-(2-thienylmethyl)benzamide hydrochloride salt. The silencing of TRPM8 expression by small interfering RNA augments the migration of PDA cells. Conversely, the activated form of TRPM8 inhibits PDA cell motility.An unglycosylated TRPM8 protein is expressed and is functional in the membrane of PDA cells. Transient receptor potential melastatin 8 inhibits the migration of PDA cells, suggesting a putative role as a biomarker or target for this channel for PDA therapy.