Abstract
The transient receptor potential melastatin-subfamily member 8 (TRPM8) channels control Ca2+ homeostasis. Recent studies indicate that TRPM8 channels are aberrantly expressed and required for cellular proliferation in pancreatic adenocarcinoma. However, the functional significance of TRPM8 in pancreatic tissues is mostly unknown. The objectives of this study are to examine the expression of TRPM8 in various histopathological types of pancreatic tissues, determine its clinical significance in pancreatic adenocarcinoma, and investigate its functional role in cancer cells invasion. We present evidence that, in normal pancreatic tissues, anti-TRPM8 immunoreactivity is detected in the centroacinar cells and the islet endocrine cells. In pre-malignant pancreatic tissues and malignant neoplasms, TRPM8 is aberrantly expressed to variable extents. In the majority of pancreatic adenocarcinoma, TRPM8 is expressed at moderate or high levels, and anti-TRPM8 immunoreactivity positively correlates with the primary tumor size and stage. In the pancreatic adenocarcinoma cell lines that express relatively high levels of TRPM8, short hairpin RNA-mediated interference of TRPM8 expression impaired their ability of invasion. These data suggest that aberrantly expressed TRPM8 channels play contributory roles in pancreatic tumor growth and metastasis, and support exploration of TRPM8 as a biomarker and target of pancreatic adenocarcinoma.
Highlights
The goal of this study is to elucidate the clinical and functional significance of the transient receptor potential transient receptor potential melastatin-subfamily member 8 (TRPM8) ion channel in pancreatic cancer
Tissue microarrays from human pancreas were examined for expression of TRPM8 by IHC using specific anti-TRPM8 antibodies
We examined the expression of TRPM8 in human pancreatic tissues by immunohistochemistry and investigated its role in pancreatic cancer cells invasion
Summary
The goal of this study is to elucidate the clinical and functional significance of the transient receptor potential TRPM8 ion channel in pancreatic cancer. For the majority of patients with pancreatic adenocarcinoma, the disease is often diagnosed at the advanced stages, when palliative systemic chemotherapy may provide limited benefits. Development of biomarkers-based targeted agents has been under active investigation, and such therapeutics may offer new opportunities to improve treatment response in patients with pancreatic cancer [2]. Accumulating evidence has revealed the important roles of ion channels in cancer including those of the transient receptor potential (TRP) family [3,4]. Certain members of the TRP melastatin (TRPM) subfamily of ion channels are implicated in various human malignancies, and their expression and roles in pancreatic cancer have recently been identified [5,6]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
