Journal
NATURE CELL BIOLOGY
Volume 2, Issue 10, Pages 737-744Publisher
MACMILLAN PUBLISHERS LTD
DOI: 10.1038/35036374
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Funding
- NCI NIH HHS [P01 CA072006, P01 CA072006-01A10003, R01 CA057621, R01 CA057621-07] Funding Source: Medline
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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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