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Role of Urokinase-Type Plasminogen Activator Receptor in Human Glioma Invasion

  • Chapter
Book cover Brain Tumors

Part of the book series: Contemporary Cancer Research ((CCR))

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Abstract

Tumor invasion results from a coordinated interaction between proteolytic enzymes that degrade basement membranes and extracellular matrix (ECM), and adhesive proteins that participate in cell attachment and migration. Degradation of the ECM is accomplished through the integrated action of several enzyme systems, including the activation of plasminogen through the urokinase pathway to generate plasmin. Plasminogen activators (PAs) released from cancer cells also aid in generating plasmin, thereby facilitating the invasion of those cells into the surrounding tissue (22). The two types of PAs, urokinase-type plasminogen activator (uPA) and tissue-type plasminogen activator (tPA), are considered to be independent gene products with distinctive structural and functional properties. Although their protein and cDNA sequences are quite different, uPA and tPA share a major substrate (plasminogen) and specific serpin-class inhibitors, the plasminogen-activator inhibitors (PAIs). uPA is secreted as a single pro-uPA zymogen that has little plasminogen-activating activity, is independent of fibrin, and is largely receptor-bound, whereas the single-chain form of tPA is catalytically active, fibrin-dependent, and primarily intravascular. Plasmin generated by either tPA or uPA directly degrades several protein constituents of the ECM, as well as activating certain other protease zymogens and latent growth factors and releasing growth factors from their ECM binding sites (57). Of these two profibrinolytic enzymes, uPA has been studied more thoroughly in relation to tumor invasion.

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Authors and Affiliations

  1. Program of Cancer Biology, Department of Biomedical and Therapeutic Sciences, University of Illinois College of Medicine, Peoria, IL

    Sanjeeva Mohanam PhD & Jasti S. Rao PhD

  2. Program of Cancer Biology, Department of Neurosurgery, University of Illinois College of Medicine, Peoria, IL

    Jasti S. Rao PhD

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  1. Sanjeeva Mohanam PhD
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  2. Jasti S. Rao PhD
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Editors and Affiliations

  1. Department of Surgery, Duke University Medical Center, Durham, NC

    Francis Ali-Osman DSc

  2. Comprehensive Cancer Center, Duke University Medical Center, Durham, NC

    Francis Ali-Osman DSc

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© 2005 Humana Press Inc., Totowa, NJ

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Mohanam, S., Rao, J.S. (2005). Role of Urokinase-Type Plasminogen Activator Receptor in Human Glioma Invasion. In: Ali-Osman, F. (eds) Brain Tumors. Contemporary Cancer Research. Humana Press. https://doi.org/10.1385/1-59259-843-9:237

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