Expression of integrin alphaVbeta3 in pancreatic carcinoma: relation to MMP-2 activation and lymph node metastasis.
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.
Hosotani
Ryo
R
Department of Surgery and Surgical Basic Science, Graduate School of Medicine, Kyoto University, Kyoto, Japan. hoso@h8.dion.ne.jp
Kawaguchi
Michiya
M
Masui
Toshihiko
T
Koshiba
Takatomo
T
Ida
Jyun
J
Fujimoto
Koji
K
Wada
Michihiko
M
Doi
Ryuichiro
R
Imamura
Masayuki
M
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
D019030:Receptors, Vitronectin; D020778:Matrix Metalloproteinase 2