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- Title
Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis.
- Authors
Bergers, G; Brekken, R; McMahon, G; Vu, T H; Itoh, T; Tamaki, K; Tanzawa, K; Thorpe, P; Itohara, S; Werb, Z; Hanahan, D
- 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.
- Publication
Nature cell biology, 2000, Vol 2, Issue 10, p737
- ISSN
1465-7392
- Publication type
Journal Article
- DOI
10.1038/35036374