Clinical & Experimental Metastasis

, Volume 18, Issue 2, pp 111–120 | Cite as

Tissue inhibitors of metalloproteases: Regulation and biological activities

  • Gianfranco Fassina
  • Nicoletta Ferrari
  • Claudio Brigati
  • Roberto Benelli
  • Leonardo Santi
  • Douglas M. Noonan
  • Adriana Albini


A central role in tissue invasion is played by proteases that degrade extracellular matrices; in particular specific metalloproteases (MMPs) have been frequently correlated with the invasive potential of tumor cells and with the angiogenic process. MMPs are tightly regulated by molecules controlling their activation and by specific inhibitors of MMPs, known as the Tissue Inhibitors of MetalloProteases or TIMPs. Four TIMP family members are currently known. An imbalance between MMPs and TIMPs is linked to the degradation of the extracellular matrix associated with several physiologic and pathologic events including angiogenesis, invasion and metastasis. TIMPs are not only the `guardians' of tissue degradation, they are able to control cell proliferation and cell survival as well. Given the critical role that TIMPs play, it is vital to know how the expression of TIMPs is controlled. Here we review the major biological properties and the molecular regulation of the TIMP expression.

basement membrane invasion metalloproteases TIMPs 


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Copyright information

© Kluwer Academic Publishers 2000

Authors and Affiliations

  • Gianfranco Fassina
    • 1
    • 2
  • Nicoletta Ferrari
    • 3
  • Claudio Brigati
    • 3
  • Roberto Benelli
    • 1
  • Leonardo Santi
    • 4
    • 5
  • Douglas M. Noonan
    • 1
  • Adriana Albini
    • 3
  1. 1.Modulo di Progressione NeoplasticaIstituto Nazionale per la Ricerca sul CancroGenoaItaly
  2. 2.Centro di Neurofisiologia CerebraleConsiglio Nazionale delle Ricerca (CNR)GenoaItaly
  3. 3.Laboratorio di Biologia MolecolareIstituto Nazionale per la Ricerca sul CancroGenoaItaly
  4. 4.Dipartimento di Oncologia, Biologia e GeneticaUniversità di GenoaGenoaItaly
  5. 5.CBA, Centro di Biotecnologie AvanzateGenoaItaly

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