Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis

Gabriele Bergers, Rolf Brekken, Gerald McMahon, Thiennu H. Vu, Takeshi Itoh, Kazuhiko Tamaki, Kazuhiko Tanzawa, Philip Thorpe, Shigeyoshi Itohara, Zena Werb, Douglas Hanahan

Research output: Contribution to journalArticle

1998 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)737-744
Number of pages8
JournalNature Cell Biology
Volume2
Issue number10
DOIs
StatePublished - Oct 2000

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Matrix Metalloproteinase 9
Matrix Metalloproteinases
Carcinogenesis
Matrix Metalloproteinase 2
Vascular Endothelial Growth Factor A
Growth
Neoplasms
Vascular Endothelial Growth Factor Receptor
Matrix Metalloproteinase Inhibitors
Urokinase-Type Plasminogen Activator
Islets of Langerhans
Transgenic Mice

ASJC Scopus subject areas

  • Cell Biology

Cite this

Bergers, G., Brekken, R., McMahon, G., Vu, T. H., Itoh, T., Tamaki, K., ... Hanahan, D. (2000). Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis. Nature Cell Biology, 2(10), 737-744. https://doi.org/10.1038/35036374

Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis. / Bergers, Gabriele; Brekken, Rolf; McMahon, Gerald; Vu, Thiennu H.; Itoh, Takeshi; Tamaki, Kazuhiko; Tanzawa, Kazuhiko; Thorpe, Philip; Itohara, Shigeyoshi; Werb, Zena; Hanahan, Douglas.

In: Nature Cell Biology, Vol. 2, No. 10, 10.2000, p. 737-744.

Research output: Contribution to journalArticle

Bergers, G, Brekken, R, McMahon, G, Vu, TH, Itoh, T, Tamaki, K, Tanzawa, K, Thorpe, P, Itohara, S, Werb, Z & Hanahan, D 2000, 'Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis', Nature Cell Biology, vol. 2, no. 10, pp. 737-744. https://doi.org/10.1038/35036374
Bergers, Gabriele ; Brekken, Rolf ; McMahon, Gerald ; Vu, Thiennu H. ; Itoh, Takeshi ; Tamaki, Kazuhiko ; Tanzawa, Kazuhiko ; Thorpe, Philip ; Itohara, Shigeyoshi ; Werb, Zena ; Hanahan, Douglas. / Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis. In: Nature Cell Biology. 2000 ; Vol. 2, No. 10. pp. 737-744.
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