Nestin as a novel therapeutic target for pancreatic cancer via tumor angiogenesis.

Abstract	The class VI intermediate filament protein, nestin is reported to be a progenitor cell marker in various tissues. In the present study, we analyzed the expression and roles of nestin in angiogenesis of pancreatic ductal adenocarcinomas, and determined whether nestin is a potential target for inhibiting tumor angiogenesis using a gene silencing strategy. Nestin expression was detected only in small vessels, whereas CD34, CD31 and factor VIII were also expressed in large-sized blood vessels in PDAC. The number of nestin-positive vessels was approximately 20% the number of CD34-positive vessels, and the average dimension of nestin-positive vessels was approximately 75% that of CD34-positive vessels. The PCNA labeling indices of nestin-positive vessels were higher than those of CD34-positive vessels and nestin-negative vessels. Reducing nestin expression by use of siRNA targeting nestin transcripts inhibited growth of the vascular endothelial cell lines, but there was no difference in cell motility. In xenograft models, administration of siRNA targeting mouse-nestin suppressed subcutaneous human pancreatic cancer cell growth in nude mice. In conclusion, nestin was expressed in small proliferating blood vessels in pancreatic cancer tissues and may be a useful marker of angiogenesis in pancreatic ductal adenocarcinoma tissues. Furthermore, nestin is a potential novel therapeutic target in pancreatic cancers to inhibit tumor angiogenesis.
Authors	Kazuya Yamahatsu, Yoko Matsuda, Toshiyuki Ishiwata, Eiji Uchida, Zenya Naito
Journal	International journal of oncology (Int J Oncol) Vol. 40 Issue 5 Pg. 1345-57 (May 2012) ISSN: 1791-2423 [Electronic] Greece
PMID	22246533 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Antigens, CD34 Biomarkers Intermediate Filament Proteins NES protein, human Nerve Tissue Proteins Nes protein, mouse Nestin Platelet Endothelial Cell Adhesion Molecule-1 Proliferating Cell Nuclear Antigen Factor VIII
Topics	Aged Animals Antigens, CD34 (metabolism) Biomarkers (metabolism) Blood Vessels (metabolism, pathology) Carcinoma, Pancreatic Ductal (blood supply, genetics, metabolism, mortality, pathology, therapy) Cell Line, Tumor Cell Movement Cell Proliferation Factor VIII (metabolism) Female Genetic Therapy (methods) Human Umbilical Vein Endothelial Cells (metabolism) Humans Immunohistochemistry Intermediate Filament Proteins (genetics, metabolism) Kaplan-Meier Estimate Male Mice Mice, Inbred BALB C Mice, Nude Middle Aged Neovascularization, Pathologic (genetics, metabolism, pathology, prevention & control) Nerve Tissue Proteins (genetics, metabolism) Nestin Pancreatic Neoplasms (blood supply, genetics, metabolism, mortality, pathology, therapy) Platelet Endothelial Cell Adhesion Molecule-1 (metabolism) Prognosis Proliferating Cell Nuclear Antigen (metabolism) RNA Interference Time Factors Transfection Xenograft Model Antitumor Assays

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