title: Aberrant over-expression of TRPM7 ion channels in pancreatic cancer: required for cancer cell invasion and implicated in tumor growth and metastasis.
abstract: Our previous studies in zebrafish development have led to identification of the novel roles of the transient receptor potential melastatin-subfamily member 7 (TRPM7) ion channels in human pancreatic cancer. However, the biological significance of TRPM7 channels in pancreatic neoplasms was mostly unexplored. In this study, we determined the expression levels of TRPM7 in pancreatic tissue microarrays and correlated these measurements in pancreatic adenocarcinoma with the clinicopathological features. We also investigated the role of TRPM7 channels in pancreatic cancer cell invasion using the Matrigel(TM)-coated transwell assay. In normal pancreas, TRPM7 is expressed at a discernable level in the ductal cells and centroacinar cells and at a relatively high level in the islet endocrine cells. In chronic pancreatitis, pre-malignant tissues, and malignant neoplasms, there is variable expression of TRPM7. In the majority of pancreatic adenocarcinoma specimens examined, TRPM7 is expressed at either moderate-level or high-level. Anti-TRPM7 immunoreactivity in pancreatic adenocarcinoma significantly correlates with the size and stages of tumors. In human pancreatic adenocarcinoma cells in which TRPM7 is highly expressed, short hairpin RNA-mediated suppression of TRPM7 impairs cell invasion. The results demonstrate that TRPM7 channels are over-expressed in a proportion of the pre-malignant lesions and malignant tumors of the pancreas, and they are necessary for invasion by pancreatic cancer cells. We propose that TRPM7 channels play important roles in development and progression of pancreatic neoplasm, and they may be explored as clinical biomarkers and targets for its prevention and treatment.
authors.affiliation: 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 nyee@hmc.psu.edu.
authors.forename: Nelson S
authors.initials: NS
authors.lastname: Yee
authors.affiliation: 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.
authors.forename: Abid A
authors.initials: AA
authors.lastname: Kazi
authors.affiliation: 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.
authors.forename: Qin
authors.initials: Q
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Zhaohai
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Division of Biostatistics and Bioinformatics, Department of Public Health, Penn State College of Medicine, Pennsylvania State University, Hershey, PA 17033, USA.
authors.forename: Arthur
authors.initials: A
authors.lastname: Berg
authors.affiliation: Schreyer Honors College, Pennsylvania State University, University Park, PA 16802, USA, Penn State Harrisburg School of Humanities, Pennsylvania State University, Middletown, PA 17057, USA.
authors.forename: Rosemary K
authors.initials: RK
authors.lastname: Yee
keywords: Biomarker; Invasion; Ion channel; Pancreatic cancer; TRPM7; Target