Glucose transporter-1 gene expression is associated with pancreatic cancer invasiveness and MMP-2 activity

Hiromichi Ito, Mark Duxbury, Michael J. Zinner, Stanley W. Ashley, Edward E. Whang

Research output: Contribution to journalArticlepeer-review

Abstract

Overexpression of the facilitative glucose transporter-1 (GLUT-1) has been observed for a wide range of human cancers, with the degree of overexpression generally being inversely correlated with prognosis. We tested the effects of modulating GLUT-1 expression on pancreatic cancer cellular invasiveness.GLUT-1 expression in MIAPaCa-2, PANC-1, BXPC-3, and CAPAN-2 cells was assayed using Western blotting. Cells were stably transfected with a GLUT-1 expression vector or a GLUT-1 RNA interference vector to alter GLUT-1 expression. Matrix metalloproteinase-2 (MMP-2) activity and expression were assayed using zymography and Western blotting, respectively. In vitro cellular invasiveness was assayed using Matrigel Boyden chambers, and in vivo metastatic potential was assessed using a nude mouse xenograft model.Variable baseline GLUT-1 expression levels were detected among the cell lines. Forced overexpression of GLUT-1 induced increases in MMP-2 expression and activity and in cellular invasiveness. GLUT-1 silencing induced reductions in MMP-2 expression and activity, cellular invasiveness, and metastatic potential in vivo.GLUT-1 promotes pancreatic cellular invasiveness. The therapeutic implications of this finding warrant further study.

Original languageEnglish (US)
Pages (from-to)548-556
Number of pages9
JournalSurgery
Volume136
Issue number3
DOIs
StatePublished - Sep 1 2004

ASJC Scopus subject areas

  • Surgery

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