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21 - Function and Expression of the uPA/uPAR System in Cancer Metastasis

from SYSTEMIC FACTORS

Published online by Cambridge University Press:  05 June 2012

By
Julio A. Aguirre-Ghiso ,
Daniel F. Alonso  and
Eduardo F. Farias
Edited by
David Lyden ,
Danny R. Welch  and
Bethan Psaila
Julio A. Aguirre-Ghiso
Affiliation:
Mount Sinai School of Medicine, United States
Daniel F. Alonso
Affiliation:
National University of Quilmes, Argentina
Eduardo F. Farias
Affiliation:
Mount Sinai School of Medicine, United States
David Lyden
Affiliation:
Weill Cornell Medical College, New York
Danny R. Welch
Affiliation:
Weill Cornell Medical College, New York
Bethan Psaila
Affiliation:
Imperial College of Medicine, London
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Summary

Metastatic disease is responsible for most cancer lethality; therefore, understanding the intricate interplay among tumor cells, soluble factors, extracellular matrix (ECM), and host cells during cancer progression to metastasis is crucial to designing successful therapies [1]. Metastasis is formed when a cell, or a group of cells, leaves the original site of the primary tumor and establishes a new colony of tumor cells in a distant, anatomically separate, site in the body [1]. To form an overt metastasis, the cells must overcome the regulatory and physical constraints imposed by the tissue milieu and initiate proliferation and invasive growth. Proteases and their inhibitors and receptors, such as those that comprise the urokinase-type plasminogen activator (uPA) system, play a crucial role in determining the ability of tumor cells to metastasize (Figure 21.1). Interestingly, dissemination of tumor cells and metastatic growth promoted by uPA and its receptor (uPAR) may be caused not only by proteolysis but also by novel functions related to cell signaling necessary for tumor cells to migrate, survive, and proliferate in target organs [1, 2]. The role of uPAR in regulating cell motility, which appears to operate similarly in normal and tumor cells, has been covered recently in extensive reviews [3]. This chapter focuses on recent advances that focus on how the uPA system coordinates proteolysis and signal transduction for invasion, dissemination, survival, and mitogenesis during tumor progression.

Type
Chapter
Information
Cancer Metastasis
Biologic Basis and Therapeutics
 , pp. 223 - 236
Publisher: Cambridge University Press
Print publication year: 2011

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