Aberrant over-expression of TRPM7 ion channels in pancreatic cancer: required for cancer cell invasion and implicated in tumor growth and metastasis

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 une...

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Main Authors: Nelson S. Yee, Abid A. Kazi, Qin Li, Zhaohai Yang, Arthur Berg, Rosemary K. Yee
Format: Article
Language:English
Published: The Company of Biologists 2015-03-01
Series:Biology Open
Subjects:
Online Access:http://bio.biologists.org/content/4/4/507
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author Nelson S. Yee
Abid A. Kazi
Qin Li
Zhaohai Yang
Arthur Berg
Rosemary K. Yee
author_facet Nelson S. Yee
Abid A. Kazi
Qin Li
Zhaohai Yang
Arthur Berg
Rosemary K. Yee
author_sort Nelson S. Yee
collection DOAJ
description 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 MatrigelTM-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.
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spelling doaj.art-16c0cd96138d4733b2dd474ee583447d2022-12-21T19:23:13ZengThe Company of BiologistsBiology Open2046-63902015-03-014450751410.1242/bio.2013708820137088Aberrant over-expression of TRPM7 ion channels in pancreatic cancer: required for cancer cell invasion and implicated in tumor growth and metastasisNelson S. Yee0Abid A. Kazi1Qin Li2Zhaohai Yang3Arthur Berg4Rosemary K. Yee5 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 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 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 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 Division of Biostatistics and Bioinformatics, Department of Public Health, Penn State College of Medicine, Pennsylvania State University, Hershey, PA 17033, USA Schreyer Honors College, Pennsylvania State University, University Park, PA 16802, USA, Penn State Harrisburg School of Humanities, Pennsylvania State University, Middletown, PA 17057, USA 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 MatrigelTM-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.http://bio.biologists.org/content/4/4/507TRPM7Ion channelPancreatic cancerInvasionBiomarkerTarget
spellingShingle Nelson S. Yee
Abid A. Kazi
Qin Li
Zhaohai Yang
Arthur Berg
Rosemary K. Yee
Aberrant over-expression of TRPM7 ion channels in pancreatic cancer: required for cancer cell invasion and implicated in tumor growth and metastasis
Biology Open
TRPM7
Ion channel
Pancreatic cancer
Invasion
Biomarker
Target
title Aberrant over-expression of TRPM7 ion channels in pancreatic cancer: required for cancer cell invasion and implicated in tumor growth and metastasis
title_full Aberrant over-expression of TRPM7 ion channels in pancreatic cancer: required for cancer cell invasion and implicated in tumor growth and metastasis
title_fullStr Aberrant over-expression of TRPM7 ion channels in pancreatic cancer: required for cancer cell invasion and implicated in tumor growth and metastasis
title_full_unstemmed Aberrant over-expression of TRPM7 ion channels in pancreatic cancer: required for cancer cell invasion and implicated in tumor growth and metastasis
title_short Aberrant over-expression of TRPM7 ion channels in pancreatic cancer: required for cancer cell invasion and implicated in tumor growth and metastasis
title_sort aberrant over expression of trpm7 ion channels in pancreatic cancer required for cancer cell invasion and implicated in tumor growth and metastasis
topic TRPM7
Ion channel
Pancreatic cancer
Invasion
Biomarker
Target
url http://bio.biologists.org/content/4/4/507
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