Matrix Metalloproteinases and the Plasminogen System in Tumor Progression

  • Yves A. DeClerck
  • Walter E. Laug


Extracellular proteases play an important contributory role in cancer progression. Proteases are expressed by tumor and stromal cells in the tumor microenvironment, where they proteolytically modify a large variety of extracellular proteins. The mechanisms by which they contribute to tumor progression are multiple and becoming increasingly complex. By degrading proteins that constitute the extracellular matrix (ECM), proteases promote the invasion of tumor cells into surrounding tissues and blood vessels and contribute to the development of distant metastases. They also play a positive role in angiogenesis by promoting the penetration of malignant tissues by endothelial cells. The proteolytic spectrum of these proteases is, however, not restricted to ECM proteins as many proteins that control critical cellular functions such as cell adhesion, growth and survival, like growth factors, cell surface receptors and growth factor binding proteins, are also the target of these proteases. Among the multiple proteases that play a key role in cancer progression are the matrix metalloproteinases (MMPs) and the plasminogen activator-plasmin (PA) system referred here as the plasminogen system. The contribution of these proteases to cancer has been the subject of an abundant scientific literature. However, these two families of proteases have often been studied independently of each other and it is uncertain whether their function in cancer overlaps in a redundant or complementary manner. In this article, interactive aspects between MMPs and the plasminogen system will be discussed first at a biochemical level. How these interactions could play a role in cancer biology will then be reviewed. Because the biochemistry of the plasminogen system is discussed in detail in other chapters, it will not be reviewed here.


Stromal Cell Human Melanoma Cell Lewis Lung Carcinoma Lewis Lung Carcinoma Cell Interstitial Collagenase 
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 2003

Authors and Affiliations

  • Yves A. DeClerck
    • 1
    • 2
  • Walter E. Laug
    • 1
    • 2
  1. 1.Division of Hematology-Oncology and Departments of Pediatrics and Biochemistry and Molecular BiologyChildrens Hospital Los AngelesLos AngelesUSA
  2. 2.USC Keck School of MedicineLos AngelesUSA

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