References
Query Results -- Details
MGI Accession ID: MGI:1891583
J Number: J:65019
Other Accession IDs:
Title: Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis
Authors: Bergers G; Brekken R; McMahon G; Vu TH; Itoh T; Tamaki K; Tanzawa K; Thorpe P; Itohara S; Werb Z; Hanahan D
Journal: Nat Cell Biol
Volume: 2
Issue: 10
Date: 2000 Oct
Year: 2000
Pages: 737-44
Review Status: Peer Reviewed
Abstract:
During carcinogenesis of pancreatic islets in transgenic mice, an angiogenic switch activates the quiescent vasculature. Paradoxically, vascular endothelial growth factor (VEGF) and its receptors are expressed constitutively. Nevertheless, a synthetic inhibitor (SU5416) of VEGF signalling impairs angiogenic switching and tumour growth. Two metalloproteinases, MMP-2/gelatinase-A and MMP-9/gelatinase-B, are upregulated in angiogenic lesions. MMP-9 can render normal islets angiogenic, releasing VEGF. MMP inhibitors reduce angiogenic switching, and tumour number and growth, as does genetic ablation of MMP-9. Absence of MMP-2 does not impair induction of angiogenesis, but retards tumour growth, whereas lack of urokinase has no effect. Our results show that MMP-9 is a component of the angiogenic switch.
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