Modulation of Endothelial Cell Migration by Heparanase
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概要
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Cancer cells need new angiogenesis to grow and invade into new areas.A currently accepted model of angiogenesis associated with cancers involves growthfactors, such as fibroblast growth factor (FGF) and vascular endothelial growth factor(VEGF), produced or induced by cancers stimulating endothelial cells in the surroundingtissue to from new blood vessels. Other molecules could also participate in the mechanismof angiogenesis by modulating growth factor activities. Heparan sulfate proteoglycan(HSPG) functions as one of such molecule by specifically binding to FGF andVEGF.Heparanase, an endo-fi-glucuronidase specifically degrading HSPG, has been reportedin some cancers and implicated in the mechanism of metastasis. Since heparanasedegrades HSPG and thus could modulate FGF and VEGF activities, the potential role ofthis enzyme in angiogenic mechanism was investigated. The migration of humanumbilical vein endothelial cells (HUVECs) toward FGF and VEGF in the Boydenchamber was employed as a model system of angiogenesis. Addition of purified heparanaseprotein to the HUVEC culture significantly abrogated the FGF- and VEGF-inducedcell migration. Reversal of this inhibitory activity of heparanase by heparinsuggested that the effect involved degradation of HSPG. HUVEC transiently transfectedwith heparanase gene also exhibited suppressed migration toward FGF and VEGF.These results clearly demonstrated that heparanase in amounts sufficient to degrade cellsurface HSPG abrogated the migration of HUVEC induced by FGF or VEGF_ Themodulation of growth factor activities using heparanase may provide useful toolsdevising new cancer therapies.
- 秋田大学の論文