Aspirin inhibits highly invasive prostate cancer cells

  • Authors:
    • Frank P. Lloyd
    • Veronika Slivova
    • Tatiana Valachovicova
    • Daniel Sliva
  • View Affiliations

  • Published online on: November 1, 2003     https://doi.org/10.3892/ijo.23.5.1277
  • Pages: 1277-1283
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Abstract

Cell adhesion, proteolytic degradation and cell migration are interrelated processes responsible for the invasion and metastasis of cancer. 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-κB) is responsible for the increased secretion of uPA and that inhibition of NF-κB 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-κB, 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 α3β1 integrin receptor, and to vitronectin (VN), which binds to αvβ3 integrin receptor. Altogether, our data suggests that aspirin inhibits the formation of uPA-uPAR-FN-α3β1 and uPA-uPAR-VN-αvβ3 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.

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November 2003
Volume 23 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Lloyd FP, Slivova V, Valachovicova T and Sliva D: Aspirin inhibits highly invasive prostate cancer cells. Int J Oncol 23: 1277-1283, 2003.
APA
Lloyd, F.P., Slivova, V., Valachovicova, T., & Sliva, D. (2003). Aspirin inhibits highly invasive prostate cancer cells. International Journal of Oncology, 23, 1277-1283. https://doi.org/10.3892/ijo.23.5.1277
MLA
Lloyd, F. P., Slivova, V., Valachovicova, T., Sliva, D."Aspirin inhibits highly invasive prostate cancer cells". International Journal of Oncology 23.5 (2003): 1277-1283.
Chicago
Lloyd, F. P., Slivova, V., Valachovicova, T., Sliva, D."Aspirin inhibits highly invasive prostate cancer cells". International Journal of Oncology 23, no. 5 (2003): 1277-1283. https://doi.org/10.3892/ijo.23.5.1277