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Tumors of the Central Nervous System, Volume 7 pp 47–57Cite as

Meningioma: Urokinase Plasminogen Activator

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Part of the book series: Tumors of the Central Nervous System ((TCNS,volume 7))

Abstract

Meningiomas, which arise from the meninges, are by far the most frequently occurring intracranial primary tumors in adults. Histopathological and clinical variants of meningiomas offer new challenges in diagnosis, pathology and treatment modalities. Moreover, recurrence of the more aggressive tumors demand the development of novel, targeted therapeutic strategies. Significant progress has been made in recent years in delineating the molecular mechanisms involved in meningioma formation, growth, and malignant progression. However, many questions remain unanswered. A different approach to the molecular genetics of meningiomas is to examine some aspects of carcinogenesis that are not necessarily specific to meningiomas. To that end, current literature demonstrates that the expression and cleavage of urokinase plasminogen activator (uPA) plays an important role in the tumorigenicity of brain tumors, and high endogenous levels of uPA are associated with advanced metastatic/invasive cancers. Extracellular matrix (ECM) degradation has been implicated as a key step in this process and is mediated by different classes of proteinases among which the uPA system plays a central role. In addition to its role in tumor propagation by binding to uPAR, uPA promotes proteolysis of plasminogen and activates matrix metalloproteinases (MMPs) and transduces signals affecting chemotactic, adhesive and mitgoenic properties of cancer cells. Recent studies have revealed that the targeted silencing of uPA and its receptor uPAR impedes the aggressive characteristics of gliomas and meningiomas. In the present article, we review the salient features of pericellular proteases (with a focus on the uPA system), the possible signaling mechanisms involved, and the therapeutic usefulness of uPA knockdown in the management of meningiomas.

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Acknowledgements

We thank Shellee Abraham for manuscript preparation. We thank Diana Meister and Sushma Jasti for manuscript review.

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Authors and Affiliations

  1. Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine, Peoria, IL, 61605, USA

    Venkateswara Rao Gogineni, Arun Kumar Nalla & Jasti S. Rao

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  1. Venkateswara Rao Gogineni
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  2. Arun Kumar Nalla
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  3. Jasti S. Rao
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Correspondence to Jasti S. Rao .

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  1. , Kean University, Room 213, Library building, Morris Avenue 1000, Union, 07083, New Jersey, USA

    M.A. Hayat

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Gogineni, V.R., Nalla, A.K., Rao, J.S. (2012). Meningioma: Urokinase Plasminogen Activator. In: Hayat, M. (eds) Tumors of the Central Nervous System, Volume 7. Tumors of the Central Nervous System, vol 7. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-2894-3_6

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  • DOI: https://doi.org/10.1007/978-94-007-2894-3_6

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