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Apoptosis

, Volume 6, Issue 6, pp 479–482 | Cite as

Tissue inhibitors of metalloproteinases and programmed cell death: Conundrums, controversies and potential implications

  • F. Mannello
  • G. Gazzanelli
Article

Abstract

Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases, which can synergistically degrade the major components of extracellular matrix (ECM). A key role in maintaining the balance between ECM deposition and degradation in several physio-pathological processes is carried out, through multiple biological functions, by four members of the tissue inhibitors of metalloproteinases (TIMPs) family. TIMP-1 and TIMP-2 are capable of inhibiting the activities of MMPs, can inhibit tumour growth, invasion and metastasis, exhibit growth factor-like activity, can inhibit angiogenesis and suppress programmed cell death (PCD) independently of the MMP-inhibitory activity. TIMP-3 is the only member which is tightly bound to ECM, inhibits TNF-α converting enzyme and induces PCD through the stabilization of TNF-α receptors on the cell surface. TIMP-4 plays a role in ECM homeostasis in a tissue-specific fashion and its overexpression induces PCD. The aim of this article is to review the exciting and intriguing literature on TIMPs, with special emphasis on their conflicting-paradoxical roles in PCD and their potential clinical usefulness.

matrix metalloproteases programmed cell death tissue inhibitors of metalloproteases 

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Copyright information

© Kluwer Academic Publishers 2001

Authors and Affiliations

  • F. Mannello
    • 1
  • G. Gazzanelli
    • 2
  1. 1.Istituto di Istologia e Analisi di Laboratorio, Facoltà di Scienze MFNUniversità degli StudiUrbinoItaly
  2. 2.Istituto di Istologia e Analisi di Laboratorio, Facoltà di Scienze MFNUniversità degli StudiUrbinoItaly

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