Delineating Protease Functions During 
Cancer Development

  • Nesrine I. Affara
  • Pauline Andreu
  • Lisa M. CoussensEmail author
Part of the Methods in Molecular Biology™ book series (MIMB, volume 539)


Much progress has been made in understanding how matrix remodeling proteases, including metalloproteinases, serine proteases, and cysteine cathepsins, functionally contribute to cancer development. In addition to modulating extracellular matrix metabolism, proteases provide a significant protumor advantage to developing neoplasms through their ability to modulate bioavailability of growth and proangiogenic factors, regulation of bioactive chemokines and cytokines, and processing of cell–cell and cell–matrix adhesion molecules. Although some proteases directly regulate these events, it is now evident that some proteases indirectly contribute to cancer development by regulating posttranslational activation of latent zymogens that then directly impart regulatory information. Thus, many proteases act in a cascade-like manner and exert their functionality as part of a proteolytic pathway rather than simply functioning individually. Delineating the cascade of enzymatic activities contributing to overall proteolysis during carcinogenesis may identify rate-limiting steps or pathways that can be targeted with anti-cancer therapeutics. This chapter highlights recent insights into the complexity of roles played by pericellular and intracellular proteases by examining mechanistic studies as well as the roles of individual protease gene functions in various organ-specific mouse models of cancer development, with an emphasis on intersecting proteolytic activities that amplify programming of tissues to foster neoplastic development.

Key words

ADAMs Angiogenesis Cysteine cathepsins Cancer ECM remodeling Inflammation Metalloproteinases Mouse models Plasminogen activators Proteases Proteolytic cascades Serine proteases 



The authors acknowledge all the scientists who made contributions to the areas of research reviewed here that were not cited due to space constraints. The authors acknowledge support from the National Institutes of Health and a Department of Defense Era of Hope Scholar Award to LMC.


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Copyright information

© Humana Press, a part of Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Nesrine I. Affara
  • Pauline Andreu
  • Lisa M. Coussens
    • 1
    Email author
  1. 1.Department of Pathology and Comprehensive Cancer CenterUniversity of CaliforniaSan Francisco

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