Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis
Author: ["Gabriele Bergers","Rolf Brekken","Gerald McMahon","Thiennu H. Vu","Takeshi Itoh","Kazuhiko Tamaki","Kazuhiko Tanzawa","Philip Thorpe","Shigeyoshi Itohara","Zena Werb","Douglas Hanahan"]
Publication: Nature Cell Biology
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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.
Cite this article
Bergers, G., Brekken, R., McMahon, G. et al. Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis. Nat Cell Biol 2, 737–744 (2000). https://doi.org/10.1038/35036374
