Aberrantly Over-Expressed TRPM8 Channels in Pancreatic Adenocarcinoma: Correlation with Tumor Size/Stage and Requirement for Cancer Cells Invasion

Cells

Nelson S. Yee²  Qin Li²  Abid A. Kazi²  Zhaohai Yang¹  Arthur Berg³ 

[1] Division of Anatomic Pathology, Department of Pathology, Penn State College of Medicine, Penn State Milton S. Hershey Medical Center, Pennsylvania State University, Hershey, PA 17033, USA; E-Mail:;Division of Hematology-Oncology, Department of Medicine, Penn State College of Medicine, Program of Experimental Therapeutics, Penn State Hershey Cancer Institute, Penn State Milton S. Hershey Medical Center, Pennsylvania State University, Hershey, PA 17033, USA; E-Mails:;Division of Biostatistics, Department of Public Health, Penn State College of Medicine, Penn State Milton S. Hershey Medical Center, Pennsylvania State University, Hershey, PA 17033, USA; E-Mail:

关键词: biomarker;    cell invasion;    cell migration;    ion channel;    molecular target;    pancreatic cancer;    TRPM8;    transient receptor potential;   

DOI  :  10.3390/cells3020500

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.