title: 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.affiliation: Departments of Pathology and Integrative Oncological Pathology,                     Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Yamahatsu
authors.forename: Yoko
authors.initials: Y
authors.lastname: Matsuda
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Ishiwata
authors.forename: Eiji
authors.initials: E
authors.lastname: Uchida
authors.forename: Zenya
authors.initials: Z
authors.lastname: Naito
mesh_terms: D000368:Aged; D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001808:Blood Vessels / Q000378:metabolism* / Q000473:pathology; D021441:Carcinoma, Pancreatic Ductal / Q000098:blood supply / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D005169:Factor VIII / Q000378:metabolism; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007381:Intermediate Filament Proteins / Q000235:genetics / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D064231:Nestin; D010190:Pancreatic Neoplasms / Q000098:blood supply / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011379:Prognosis; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D034622:RNA Interference; D013997:Time Factors; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
chemical_list: D018952:Antigens, CD34; D015415:Biomarkers; D007381:Intermediate Filament Proteins; C577484:NES protein, human; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D018809:Proliferating Cell Nuclear Antigen; D005169:Factor VIII