You are here

Article Text

Article menu
Download PDFPDF
LEADING ARTICLE
Matrix metalloproteinases in gastrointestinal cancer
  1. P D BROWN
  1. Department of Clinical Research,
  2. British Biotech Pharmaceuticals Ltd,
  3. Watlington Road, Oxford, OX4 5LY, UK
  4. email: brownp@britbio.co.uk

https://doi.org/10.1136/gut.43.2.161

Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

    Matrix metalloproteinases (MMPs) are a family of enzymes that are responsible for the breakdown of connective tissue proteins. These enzymes play a central role in tissue remodelling associated with growth, development and repair. In these physiological processes MMP activity is tightly regulated. However, it is clear that aberrant MMP expression can contribute to the pathogenesis of several diseases including rheumatoid arthritis, tumour invasion and metastasis, multiple sclerosis, cerebral haemorrhage, and inflammatory bowel disease. The focus of this short article is the expression of MMP activity in gastrointestinal cancer. Rather than provide a complete overview of research in this area the article will consider areas of particular clinical relevance, such as the potential use of MMPs as prognostic markers and the use of MMP inhibitors in the treatment of cancer. For further insight into the role of MMPs in tumour invasion and metastasis the reader is referred to the recent review by Chambers and Matrisian.1

    Matrix metalloproteinases

    Sixteen MMPs have been identified to date1 (MMPs 1–19, numbers 4–6 were not used). The enzymes are structurally related and take their name from a zinc atom in the active site. The enzymes range from the well characterised interstitial collagenase (MMP-1) which degrades fibrillar collagens, to the more obscure membrane-type (MT-) MMPs whose functions and substrates are still largely to be defined. As might be expected for enzymes with such destructive potential the activity of MMPs is tightly regulated at several levels. Some MMPs do seem to be expressed constitutively in normal tissues (for example, progelatinase A in vascular smooth muscle) but in general their expression is linked to active processes of tissue remodelling such as trophoblast implantation or mammary gland involution. The enzymes are secreted in an inactive proform with an amino-terminal domain blocking the active site.2 In most cases removal of …

    View Full Text

    Footnotes

    • Leading articles express the views of the author and not those of the editor and editorial board.