And how PAI 1 is related to the increased metastasis in human cancers? Detailed answers appreciated.
The main components of the urokinase plasminogen activator (uPA) system include the serine protease, uPA, 2 serpin inhibitors, PAI-1 and PAI-2 and the membrane-linked receptor uPAR. Extensive data from model systems has shown that the uPA system plays a key role in cancer invasion and metastasis.
The urokinase receptor (uPAR) binds inactive urokinase (pro-uPA), which is then converted to active uPA. Active uPA proteolytically converts the inactive zymogen plasminogen to active plasmin, which then breaks down ECM components or activates latent growth factors such as transforming growth factor 1 (TGF-1). Plasmin can also degrade the ECM indirectly through activation of pro-matrix metalloproteinases (MMPs). Degradation of ECM is a prerequisite for tumor invasion and metastasis.
The role of uPA in the process of cancer spread is achieved through the ability of uPA to modulate cell adhesion and stimulate angiogenesis, mitogenesis, and cell migration. It is also shown that uPA prevents apoptosis, thereby increasing the survival of malignant cells.
Plasminogen activator inhibitors are anti-proteases that inhibit uPA and tPA.
As uPA has been shown to be associated with poor prognosis in cancer it would be reasonable to assume that PAI-1 would protect the organism from tumor growth. However, it has been shown that PAI-1 is of importance for tumor angiogenesis and correlates with poor prognosis. It acts through other signal pathways, thereby promoting tumor growth.
Thank you very much madam for your valuable answer, still its is not clear to me that what makes the uPA to get activated in cancer cells (activator), and once the ECM gets degraded , what makes the adjacent (normal) cell to become a cancerous one....
I believe PAI-1 may have roles in regulating cancer cell interaction with matrix proteins, a critical step in mediating cancer metastasis.
Thank you all for the informative replies.. Thanks for the articles...
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