BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: GLUT-1 promotes pancreatic cellular invasiveness. The therapeutic implications of this finding warrant further study.
BACKGROUND: Overexpression of the facilitative glucose transporter-1 (GLUT-1) has been observed for a wide range of humancancers, 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. METHODS: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. RESULTS: 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. CONCLUSION:GLUT-1 promotes pancreatic cellular invasiveness. The therapeutic implications of this finding warrant further study.
Authors: Maciej Serda; Matthew J Ware; Jared M Newton; Sanchit Sachdeva; Martyna Krzykawska-Serda; Lam Nguyen; Justin Law; Andrew O Anderson; Steven A Curley; Lon J Wilson; Stuart J Corr Journal: Nanomedicine (Lond) Date: 2018-12-03 Impact factor: 5.307
Authors: L D Kellenberger; J E Bruin; J Greenaway; N E Campbell; R A Moorehead; A C Holloway; J Petrik Journal: J Oncol Date: 2010-02-17 Impact factor: 4.375