title: Expression of integrin alphaVbeta3 in pancreatic carcinoma: relation to MMP-2 activation and lymph node metastasis.
abstract: BACKGROUND
  Overexpression of integrin alphaVbeta3 had been demonstrated in various tumors. Studies have suggested that elevated levels of integrin alphaVbeta3 in melanoma cells are deeply involved in the mechanism of increased melanoma invasiveness.
  
  
  OBJECTIVE
  To examine the expression of integrin alphaVbeta3 in pancreatic carcinoma and to evaluate the correlation between integrin expression accompanied by MMP-2 activation and clinicopathologic factors.
  
  
  METHODS
  Integrin alphaVbeta3 specific antibody LM-609 was used for immunochemical analysis, and intracellular localization was determined in human pancreatic cancer cell lines cultured on vitronectin coating. Fifty pancreatic adenocarcinomas analyzed immunohistochemically and 26 frozen samples were analyzed gelatin-zymographically.
  
  
  RESULTS
  Two of three pancreatic cancer cell lines demonstrated integrin alphaVbeta3 immunofluorescence with a membranous pattern, and 29 of 50 pancreatic carcinomas showed positive immunostaining of tumor cells. There was no significant correlation between integrin alphaVbeta3 expression and tumor size, tumor grade, or peripancreatic invasion. However, primary tumors with lymph node metastasis featured significantly higher expression of integrin alphaVbeta3 than those without node metastasis. Tumors with high integrin alphaVbeta3 expression showed significantly higher MMP-2 activation ratios than did tumors with low expression.
  
  
  CONCLUSIONS
  Expression analysis in pancreatic cancer tissue demonstrated involvement of alphaVbeta3 integrin in lymph node metastasis rather than peripancreatic invasion. MMP-2 activation is linked, at least in part, to the expression of integrin alphaVbeta3 of pancreatic cancer cells.
authors.affiliation: Department of Surgery and Surgical Basic Science, Graduate School of Medicine, Kyoto University, Kyoto, Japan. hoso@h8.dion.ne.jp
authors.forename: Ryo
authors.initials: R
authors.lastname: Hosotani
authors.forename: Michiya
authors.initials: M
authors.lastname: Kawaguchi
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Masui
authors.forename: Takatomo
authors.initials: T
authors.lastname: Koshiba
authors.forename: Jyun
authors.initials: J
authors.lastname: Ida
authors.forename: Koji
authors.initials: K
authors.lastname: Fujimoto
authors.forename: Michihiko
authors.initials: M
authors.lastname: Wada
authors.forename: Ryuichiro
authors.initials: R
authors.lastname: Doi
authors.forename: Masayuki
authors.initials: M
authors.lastname: Imamura
mesh_terms: D000368:Aged; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D019030:Receptors, Vitronectin / Q000096:biosynthesis*; D016019:Survival Analysis; D014407:Tumor Cells, Cultured
chemical_list: D019030:Receptors, Vitronectin; D020778:Matrix Metalloproteinase 2