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JOURNAL: International journal of oncology.; 2003 Nov;23(5) p22637
AUTHORS: Lloyd FP J; Slivova V; Valachovicova T; Sliva D;
ABSTRACT: Cell adhesion, proteolytic degradation and cell migration are interrelated
processes responsible for the invasion and metastasis of cancer.
COMMENTARY: One of the crucial molecules involved in cancer metastasis is urokinase-type
plasminogen activator (uPA). An elevated concentration of uPA is a strong
indicator of poor prognosis. In addition to the proteolytic activity of
uPA, which degrades the extracellular matrix, uPA also binds to its receptor
(uPAR) and controls cell adhesion and migration through the reorganization
of actin cytoskeleton.
We have recently demonstrated that constitutively active nuclear factor-kappa B (NF-kappa is responsible for the increased secretion of uPA and that inhibition of NF-kappaB suppresses secretion of uPA and cell migration of highly invasive cancer cells.
Aspirin and other nonsteroidal anti-inflammatory drugs have been recently shown to have a chemopreventive effect in colon and pancreatic cancers. Here we show that aspirin inhibits NF-kappaB, resulting in the suppression of uPA secretion from the highly invasive human prostate cancer cells PC-3. Furthermore, aspirin inhibited migration of PC-3 cells, suggesting an effect on the uPA-uPAR signaling complex.
Finally, aspirin suppressed adhesion of PC-3 cells to fibronectin (FN), which binds to an alpha3beta1 integrin receptor, and to vitronectin (VN), which binds to alphavbeta3 integrin receptor.
Altogether, our data suggests that aspirin inhibits the formation of uPA-uPAR-FN-alpha3beta1 and uPA-uPAR-VN-alphavbeta3 complexes, resulting in the suppression of cell adhesion and cell motility of the highly invasive prostate cancer cells PC-3. These results indicate that aspirin may contribute directly to reducing invasion and metastasis of prostate cancers by inhibiting cell migration and invasion.