Reference SummaryBergers G, Nat Cell Biol 2000 Oct;2(10):737-44

Title

 Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis

Authors

 Bergers G; Brekken R; McMahon G; Vu TH; Itoh T; Tamaki K; Tanzawa K; Thorpe P; Itohara S; Werb Z; Hanahan D

Journal

 Nat Cell Biol

Volume

 2

Issue

 10

Year

 2000

Pages

 737-44

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.

Links

 J:65019 – MGI References
11025665 – National Library of Medicine/PubMed

Strain Notes

Strain Note
B6.Cg-Tg(RIP1-Tag)2Dh The TgN(RIP1-Tag)2Dh transgene was originally generated using (C57BL/6J x DBA/2J)F2 embryos. The mice were then backcrossed to C57BL/6J.

Models
Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
B6.Cg-Tg(RIP1-Tag)2Dh Pancreas - Islet of Langerhans - Beta cell adenoma Pancreas - Islet of Langerhans - Beta cell

very high
C57BL/6-Mmp9tm1Tvu Tg(RIP1-Tag)2Dh Pancreas - Islet of Langerhans - Beta cell adenoma Pancreas - Islet of Langerhans - Beta cell

very high
C57BL/6-Mmp2tm1Ito Tg(RIP1-Tag)2Dh Pancreas - Islet of Langerhans - Beta cell adenoma Pancreas - Islet of Langerhans - Beta cell

very high
C57BL/6-Plautm1Mlg Tg(RIP1-Tag)2Dh Pancreas - Islet of Langerhans - Beta cell adenoma Pancreas - Islet of Langerhans - Beta cell

very high
B6.Cg-Tg(RIP1-Tag)2Dh Pancreas - Islet of Langerhans - Beta cell carcinoma Pancreas - Islet of Langerhans - Beta cell

very high
C57BL/6-Mmp9tm1Tvu Tg(RIP1-Tag)2Dh Pancreas - Islet of Langerhans - Beta cell carcinoma Pancreas - Islet of Langerhans - Beta cell

very high
C57BL/6-Mmp2tm1Ito Tg(RIP1-Tag)2Dh Pancreas - Islet of Langerhans - Beta cell carcinoma Pancreas - Islet of Langerhans - Beta cell

very high
C57BL/6-Plautm1Mlg Tg(RIP1-Tag)2Dh Pancreas - Islet of Langerhans - Beta cell carcinoma Pancreas - Islet of Langerhans - Beta cell

very high
B6.Cg-Tg(RIP1-Tag)2Dh Pancreas - Islet of Langerhans - Beta cell carcinoma in situ Pancreas - Islet of Langerhans - Beta cell

observed
B6.Cg-Tg(RIP1-Tag)2Dh Pancreas - Islet of Langerhans - Beta cell hyperplasia Pancreas - Islet of Langerhans - Beta cell

100
B6.Cg-Tg(RIP1-Tag)2Dh Pancreas - Islet of Langerhans - Beta cell hyperplasia
  • SU5416
 Pancreas - Islet of Langerhans - Beta cell

very high
B6.Cg-Tg(RIP1-Tag)2Dh Pancreas - Islet of Langerhans - Beta cell hyperplasia
  • batimastat (BB-94)
 Pancreas - Islet of Langerhans - Beta cell

very high
B6.Cg-Tg(RIP1-Tag)2Dh Pancreas - Islet of Langerhans - Beta cell hyperplasia
  • R94138
 Pancreas - Islet of Langerhans - Beta cell

very high
C57BL/6-Mmp9tm1Tvu Tg(RIP1-Tag)2Dh Pancreas - Islet of Langerhans - Beta cell hyperplasia Pancreas - Islet of Langerhans - Beta cell

very high
C57BL/6-Mmp2tm1Ito Tg(RIP1-Tag)2Dh Pancreas - Islet of Langerhans - Beta cell hyperplasia Pancreas - Islet of Langerhans - Beta cell

very high
C57BL/6-Plautm1Mlg Tg(RIP1-Tag)2Dh Pancreas - Islet of Langerhans - Beta cell hyperplasia Pancreas - Islet of Langerhans - Beta cell

very high
B6.Cg-Tg(RIP1-Tag)2Dh Pancreas - Islet of Langerhans - Beta cell tumor Pancreas - Islet of Langerhans - Beta cell

100
B6.Cg-Tg(RIP1-Tag)2Dh Pancreas - Islet of Langerhans - Beta cell tumor
  • SU5416
 Pancreas - Islet of Langerhans - Beta cell

very high
B6.Cg-Tg(RIP1-Tag)2Dh Pancreas - Islet of Langerhans - Beta cell tumor
  • batimastat (BB-94)
 Pancreas - Islet of Langerhans - Beta cell

very high
B6.Cg-Tg(RIP1-Tag)2Dh Pancreas - Islet of Langerhans - Beta cell tumor
  • R94138
 Pancreas - Islet of Langerhans - Beta cell

very high
C57BL/6-Mmp9tm1Tvu Tg(RIP1-Tag)2Dh Pancreas - Islet of Langerhans - Beta cell tumor Pancreas - Islet of Langerhans - Beta cell

very high
C57BL/6-Mmp2tm1Ito Tg(RIP1-Tag)2Dh Pancreas - Islet of Langerhans - Beta cell tumor Pancreas - Islet of Langerhans - Beta cell

very high
C57BL/6-Plautm1Mlg Tg(RIP1-Tag)2Dh Pancreas - Islet of Langerhans - Beta cell tumor Pancreas - Islet of Langerhans - Beta cell

very high