The urokinase plasminogen activator system in cancer: recent advances and implication for prognosis and therapy

Cancer dissemination and metastasis is synonymous with invasive cell migration; a process in which the extracellular matrix (ECM) plays the dual role of the substratum on which the cells move as well as the physical obstacle that the cells have to surpass. To degrade the physical obstacle, which the...

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Bibliographic Details
Published in:Cancer and metastasis reviews 2003-06, Vol.22 (2-3), p.205-222
Main Authors: Sidenius, Nicolai, Blasi, Francesco
Format: Article
Language:English
Subjects:
Animals
Humans
Neoplasm Invasiveness - pathology
Neoplasm Metastasis
Neoplasms - diagnosis
Neoplasms - pathology
Neoplasms - therapy
Plasminogen - metabolism
Prognosis
Receptors, Cell Surface - physiology
Receptors, Urokinase Plasminogen Activator
Signal Transduction
Urokinase-Type Plasminogen Activator - physiology
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Summary:Cancer dissemination and metastasis is synonymous with invasive cell migration; a process in which the extracellular matrix (ECM) plays the dual role of the substratum on which the cells move as well as the physical obstacle that the cells have to surpass. To degrade the physical obstacle, which the ECM poses in the direction of migration, cells use proteolytic enzymes capable of degrading the ECM components. A major protease system responsible for ECM degradation is the plasminogen activation system, which generates the potent serine protease plasmin. The subject of this review, the urokinase-type plasminogen activator (uPA) and its receptor (uPAR), plays an impressive range of distinct, but overlapping functions in the process of cancer invasion and metastasis: Firstly, uPA/uPAR promotes extracellular proteolysis by regulating plasminogen activation. Secondly, uPA/uPAR regulates cell/ECM interactions as an adhesion receptor for vitronectin (Vn) and through its capacity to modulate integrin function. Thirdly, uPA/uPAR regulates cell migration as a signal transduction molecule and by its intrinsic chemotactic activity. This review is focused on recent insight into the cancer related biology of the uPA/uPAR system as well as its implications for clinical cancer diagnosis, prognosis and therapy.
ISSN:0167-7659
1573-7233
DOI:10.1023/a:1023099415940