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Matrix Metalloproteinases in Cancer

  • Barbara Fingleton
  • Lynn M. Matrisian
Chapter
Part of the Cancer Drug Discovery and Development book series (CDD&D)

Abstract

The production of proteinase activity has long been thought to be an essential property of tumor cells that allow them to invade and metastasize to distant sites. The “three step theory of invasion” proposed by Liotta and colleagues (1) suggests that potentially invasive cells must first attach to basement membrane proteins via cell-surface receptors, i.e., the integrins. Localized, extracellular proteolytic activity then clears a path for the cell. Finally, the cell has to move into the cleared region, a locomotive process which probably depends on specific chemotactic factors. This invasion process first occurs as a tumor cell breaches the basement membrane at the primary tumor site—an event which signifies a malignant lesion. In order to result in a growth at a secondary site, the process has to be repeated as tumor cells penetrate blood vessels through a process referred to as intravasation. They can be carried to a new location, where a third invasive event must occur to extravasate into the parenchyma of the distant organ. Thus, proteolysis of basement membrane (BM) and extracellular matrix (ECM) components has been viewed as an essential step in tumor invasion and metastasis. Since metastasis is the principal cause of cancerassociated mortality, the tumor proteases responsible for BM and ECM degradation have been viewed as accessible targets for therapeutic intervention.

Keywords

Basal Cell Carcinoma Tissue Inhibitor Giant Cell Tumor Mouse Mammary Tumor Virus TIMP Level 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 2001

Authors and Affiliations

  • Barbara Fingleton
  • Lynn M. Matrisian

There are no affiliations available

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