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Metallo- Serine- Serine- Cystein- Cystein- Aspartic- Metallo- Serine- Serine- Cystein- Cystein- Aspartic- Proteinases Proteinases Garbisa 2001.

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Presentation on theme: "Metallo- Serine- Serine- Cystein- Cystein- Aspartic- Metallo- Serine- Serine- Cystein- Cystein- Aspartic- Proteinases Proteinases Garbisa 2001."— Presentation transcript:

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2 Metallo- Serine- Serine- Cystein- Cystein- Aspartic- Metallo- Serine- Serine- Cystein- Cystein- Aspartic- Proteinases Proteinases Garbisa 2001

3 kDaabbrev.instrumental to 55 interstitial collagenaseMMP-1 stromal infiltration 72 gelatinase AMMP-2 basement membr. invasion …….…………………………………….…………... 28 matrilysinMMP-7 ECM protein degradation 92 gelatinase BMMP-9 basement membr. invasion 57 stromelysin-2MMP-10 …….…………………………………….…………... 54 M metallo elastaseMMP-12 ECM protein degradation … ….…………………………………….…………... 66 membr. type 1 MMPMT1-MMP gelatinase recep./activat. …….…………………………………….… > 26 Matrix Metallo Proteinases (MMPs) Garbisa 2001

4 natural 2 -macroglobulin natural broad spectrum 2 -macroglobulin 1 -protease inhibitor 1 -protease inhibitor TIMP narrow spectrumTissue Inhibitors of Metallo Proteinases TIMP-1 TIMP-1 in vitro TIMP-2 TIMP-2 in vitro inhibition of invasion TIMP-3 TIMP-3 in vitro TIMP-4 TIMP-4 in vitro MMP Inhibitors MMP Inhibitors synthetic batimastat (BB94) synthetic batimastat (BB94)in trial/ abandoned marimastat marimastat in trial / abandoned AG3340 AG3340 in trial BAY12-9566 BAY12-9566 phase I ……………… …………………….. Garbisa 2001

5 MMPs & invasion MMP-2 (Gel.A) is instrumental to invasion & metastasis Garbisa 2001

6 MMPs & endothelial cells MMP-2 (Gel.A) is instrumental to angiogenesis Nature 398, 381, 1999 Angiogenesis inhibited by drinking tea Angiogenesis inhibited by drinking tea Y. Cao & R. Cao Nature 398, 381, 1999 Angiogenesis inhibited by drinking tea Angiogenesis inhibited by drinking tea Y. Cao & R. Cao Science 221, 281-283, 1983 Basement Membrane Collagen: Degradation by Migrating Endothelial Cells Tea Kalebic, S. Garbisa, B. Glaser, and L. A. Liotta Science 221, 281-283, 1983 Basement Membrane Collagen: Degradation by Migrating Endothelial Cells Tea Kalebic, S. Garbisa, B. Glaser, and L. A. Liotta Does EGCG inhibit gelatinases ? EGCG inhibits angiogenesis Garbisa 2001

7 MMP-2 or Gelatinase A MMP-2 or Gelatinase A MT-MMP MT-MMP Membrane Type... uPA / Pl uPA / Pl urokinase Plasminogen Activator activators cell Morgunova E. et al. Science 284, 1667, 1999MMP-2 Garbisa 2001


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