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Nat Cell Biol. 2000 Oct;2(10):737-44.

Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis.

Author information

1
Department of Biochemistry and Biophysics, University of California, 513 Parnassus Avenue, San Francisco, California 94143, USA.

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.

PMID:
11025665
PMCID:
PMC2852586
DOI:
10.1038/35036374
[Indexed for MEDLINE]
Free PMC Article

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