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Pancreas. 2014 Jul;43(5):795-800. doi: 10.1097/MPA.0000000000000106.

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

Author information

1
From the *Center of Digestive Disease and Liver Transplantation, Fundeni Clinical Institute; †Department of Molecular and Cell Biology, Romanian Academy Institute of Biochemistry; ‡Department of Anatomy, Physiology, and Biophysics, Faculty of Biology, University of Bucharest, Bucharest, Romania; §Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA; and ∥Division of Molecular Pathology, Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan.

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.

PMID:
24658318
DOI:
10.1097/MPA.0000000000000106
[Indexed for MEDLINE]

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