Characterization of functional transient receptor potential melastatin 8 channels in human pancreatic ductal adenocarcinoma cells

Dana Cucu, Gabriela Chiritoiu, Stefana Petrescu, Alexandru Babes, Luciana Stanica, Dan G. Duda, Akira Horii, Simona Olimpia Dima, Irinel Popescu

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

Abstract

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Original languageEnglish
Pages (from-to)795-800
Number of pages6
JournalPancreas
Volume43
Issue number5
DOIs
Publication statusPublished - 2014 Jul

Keywords

  • Menthol
  • Migration
  • Pancreatic adenocarcinoma
  • Transient receptor potential melastatin 8

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Hepatology
  • Endocrinology

Fingerprint Dive into the research topics of 'Characterization of functional transient receptor potential melastatin 8 channels in human pancreatic ductal adenocarcinoma cells'. Together they form a unique fingerprint.

Cite this