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 journalArticle

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 2004
Externally publishedYes

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Facilitative Glucose Transport Proteins
Matrix Metalloproteinase 2
Pancreatic Neoplasms
Gene Expression
Western Blotting
RNA Interference
Heterografts
Nude Mice
Cell Line

ASJC Scopus subject areas

  • Surgery

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Glucose transporter-1 gene expression is associated with pancreatic cancer invasiveness and MMP-2 activity. / Ito, Hiromichi; Duxbury, Mark; Zinner, Michael J.; Ashley, Stanley W.; Whang, Edward E.

In: Surgery, Vol. 136, No. 3, 09.2004, p. 548-556.

Research output: Contribution to journalArticle

Ito, Hiromichi ; Duxbury, Mark ; Zinner, Michael J. ; Ashley, Stanley W. ; Whang, Edward E. / Glucose transporter-1 gene expression is associated with pancreatic cancer invasiveness and MMP-2 activity. In: Surgery. 2004 ; Vol. 136, No. 3. pp. 548-556.
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