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Proteases as prognostic markers in cancer

BMJ 1998; 316 doi: (Published 14 March 1998) Cite this as: BMJ 1998;316:790

Proteolytic enzymes and their inhibitors influence the spread of cancer

  1. Hein W Verspaget, Associate professor
  1. Department of Gastroenterology-Hepatology, Leiden University Medical Centre, PO Box 9600, 2300 RC Leiden, Netherlands

    Papers p 829

    Just how tumours become malignant remains an enigma, despite major advances in our knowledge of genetic susceptibility, cellular derailment processes, and environmental factors. The rapid multiplication of cells in the early phase of a tumour does not usually cause serious disease so long as the growth remains confined to its original tissue boundaries. When, however, cells migrate from their original tissue compartment, invade the normal surrounding tissue, and disseminate throughout the body they have become malignant.

    The migration and invasion characteristics of malignant cells requires them to be able to cross extracellular barriers. In the primary organ these predominantly consist of basement membranes and connective tissue, collectively called the extracellular matrix. The extracellular matrix is made up of a dense network of different components including laminin, fibronectin and other glycoproteins, collagens, and proteoglycans. To invade and metastasise, tumours possess a lytic machinery made up of different proteolytic enzymes, the proteases. The main classes of proteases contributing to the lytic processes around tumours are cathepsins, plasminogen activators, and matrix metalloproteinases.1 The first evidence of the active part played by these enzymes in neoplastic disease came from studies …

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