COX-2 overexpression increases motility and invasion of breast cancer cells

  • Authors:
    • Balraj Singh
    • Jacob A. Berry
    • Angela Shoher
    • Vijay Ramakrishnan
    • Anthony Lucci
  • View Affiliations

  • Published online on: May 1, 2005     https://doi.org/10.3892/ijo.26.5.1393
  • Pages: 1393-1399
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Abstract

Cyclooxygenase-2 (COX-2), an inducible enzyme involved in prostaglandin (including PGE2) biosynthesis, is overexpressed in several epithelial malignancies including breast cancer. We tested the hypothesis that COX-2 overexpression in breast cancer cells results in increased cell motility and invasion. COX-2 overproducing cells were generated by stable transfection of several human breast cancer cells with pSG5-COX2 vector. We confirmed the overexpression of COX-2 protein by western blotting, and by measuring PGE2 in the medium with an immunoassay. We measured cell motility by counting the number of cells crossing an 8-micron pore size PET membrane, and cell invasion by counting the number of cells invading through a Matrigel-coated membrane that simulates basement membrane. COX-2 transfected MDA-231 cells produced 30-43-fold more PGE2 as compared to parental cells. COX-2 overexpression increased cell migration approximately 2.2-fold and cell invasion through Matrigel approximately 5.1-fold. Addition of 50 µM NS-398, a COX-2 inhibitor, inhibited Matrigel invasion of MDA-231 cells by 54% as compared to solvent confirming the role of COX-2 in cell invasion. It is known that an increase in cell migration and invasion can be brought about by cytoskeletal alterations and basement membrane degradation due to increased expression of pro-urokinase plasminogen activator (pro-uPA). To investigate the mechanism of our observed increase in cell invasion by COX-2, we found by western blotting that the level of pro-uPA was significantly higher (approximately 5-fold) in COX-2 transfected MDA-231 cells than untransfected MDA-231 cells. Similar to our observations in cell culture, we found evidence that increased COX-2 activity correlates with uPA in a mouse model of breast cancer metastasis to bone. In this study, we conclude that COX-2 overexpression in human breast cancer cells enhances cell motility and invasiveness thus suggesting a mechanism of COX-2 mediated metastasis.

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May 2005
Volume 26 Issue 5

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

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Copy and paste a formatted citation
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Spandidos Publications style
Singh B, Berry JA, Shoher A, Ramakrishnan V and Lucci A: COX-2 overexpression increases motility and invasion of breast cancer cells. Int J Oncol 26: 1393-1399, 2005
APA
Singh, B., Berry, J.A., Shoher, A., Ramakrishnan, V., & Lucci, A. (2005). COX-2 overexpression increases motility and invasion of breast cancer cells. International Journal of Oncology, 26, 1393-1399. https://doi.org/10.3892/ijo.26.5.1393
MLA
Singh, B., Berry, J. A., Shoher, A., Ramakrishnan, V., Lucci, A."COX-2 overexpression increases motility and invasion of breast cancer cells". International Journal of Oncology 26.5 (2005): 1393-1399.
Chicago
Singh, B., Berry, J. A., Shoher, A., Ramakrishnan, V., Lucci, A."COX-2 overexpression increases motility and invasion of breast cancer cells". International Journal of Oncology 26, no. 5 (2005): 1393-1399. https://doi.org/10.3892/ijo.26.5.1393