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New Insights on COX-2 in Chronic Inflammation Driving Breast Cancer Growth and Metastasis

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Abstract

The medicinal use of aspirin stretches back to ancient times, before it was manufactured in its pure form in the late 19th century. Its accepted mechanistic target, cyclooxygenase (COX), was discovered in the 1970s and since this landmark discovery, the therapeutic application of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) has increased dramatically. The most significant benefits of NSAIDs are in conditions involving chronic inflammation (CI). Given the recognized role of CI in cancer development, the use of long-term NSAID treatment in the prevention of cancer is an enticing possibility. COX-2 is a key driver of CI, and here we review COX-2 expression as a predictor of survival in various cancer types, including breast. Obesity and post-partum involution are natural inflammatory states that are associated with increased breast cancer risk. We outline the COX-2 mediated mechanisms contributing to the growth of cancers. We dissect the cellular mechanism of epithelial-mesenchymal transition (EMT) and how COX-2 may induce this to facilitate tumor progression. Finally we examine the potential regulation of COX-2 by c-Myb, and the possible interplay between c-Myb/COX-2 in proliferation, and hypoxia inducible factor-1 alpha (HIF1α)/COX-2 in invasive pathways in breast cancer.

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Acknowledgments

We thank Dr Kara Britt (Peter MacCallum Cancer Centre, VIC) for critiquing the manuscript. EWT was supported in part by the EMPathy National Collaborative Research Program funded by the National Breast Cancer Foundation, Australia, and National Health and Medical Research Council (NHMRC) Project Grant 1027527, CS by the Raine Foundation at the University of Western Australia, and RGR by the NHMRC. This study benefited from support by the Victorian Government’s Operational Infrastructure Support Program to St. Vincent’s Institute and the Peter MacCallum Cancer Institute.

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The authors affirm full compliance with the ethical standards outlined in the JMGBN Instructions to Authors.

Conflicts of Interest

The authors declare that they have no conflicts of interest.

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Authors and Affiliations

  1. VBCRC Invasion and Metastasis Unit, St Vincent’s Institute, Fitzroy, VIC, Australia

    Honor J. Hugo & E. W. Thompson

  2. School of Surgery, University of Western Australia, Perth, Western Australia, Australia

    C. Saunders

  3. Differentation and Transcription Laboratory, Peter MacCallum Cancer Centre and the Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, VIC, Australia

    R. G. Ramsay

  4. Institute of Health and Biomedical Innovation and School of Biomedical Sciences, Queensland Institute of Technology, Brisbane, QLD, Australia

    E. W. Thompson

  5. Department of Surgery, St Vincent’s Hospital, University of Melbourne, Melbourne, VIC, Australia

    E. W. Thompson

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  1. Honor J. Hugo
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  3. R. G. Ramsay
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  4. E. W. Thompson
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Correspondence to Honor J. Hugo.

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Hugo, H.J., Saunders, C., Ramsay, R.G. et al. New Insights on COX-2 in Chronic Inflammation Driving Breast Cancer Growth and Metastasis. J Mammary Gland Biol Neoplasia 20, 109–119 (2015). https://doi.org/10.1007/s10911-015-9333-4

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  • DOI: https://doi.org/10.1007/s10911-015-9333-4

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