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COX-2 involvement in breast cancer metastasis to bone

Abstract

Cyclooxygenase-2 (COX-2) is expressed in 40% of human invasive breast cancers. Bone is the predominant site of metastasis in case of breast cancer. We investigated the role of COX-2 in a suitable mouse model of breast cancer metastasis to bone using the whole-body luciferase imaging of cancer cells. We provide several lines of evidence that COX-2 produced in breast cancer cells is important for bone metastasis in this model including (1) COX-2 transfection enhanced the bone metastasis of MDA-435S cells and (2) breast cancer cells isolated and cultured from the bone metastases produced significantly more prostaglandin E2 (an important mediator of COX-2) than the parental injected cell populations of breast cancer cells. Next, we found that a COX-2 inhibitor, MF-tricyclic, inhibited bone metastasis caused by a bone-seeking clone both in prevention regimen (in which case mice started receiving MF-tricyclic 1 week before the injection of cancer cells) and in treatment regimen (in which case mice received MF-tricyclic after the development of bone metastasis). These studies indicate that COX-2 produced in breast cancer cells may be vital to the development of osteolytic bone metastases in patients with breast cancer, and that COX-2 inhibitors may be useful in halting this process.

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Acknowledgements

These studies were initiated when the authors were at Baylor College of Medicine, Houston, TX. We thank Richard J Kulmacz (University of Texas Health Science Center, Houston, TX, USA) for kindly providing pSG5-COX2 vector, Timothy Hla (University of Connecticut health Center, Pharmington, CT, USA) for pOSML-COX2GFP vector, and David Spencer (Baylor College of Medicine, Houston, TX) for providing the pEF1a-Luc-IRES-Neo vector and for help with the luciferase imaging of mice. These studies were supported in part by the grants from the Wendy Will Case Cancer Fund, Inc., Methodist Hospital Foundation and by the grants R21 DK067682 from the National Institutes of Health and DAMD17-03-1-0669 from the United States Army Medical Research and Material Command.

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Correspondence to A Lucci.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Singh, B., Berry, J., Shoher, A. et al. COX-2 involvement in breast cancer metastasis to bone. Oncogene 26, 3789–3796 (2007). https://doi.org/10.1038/sj.onc.1210154

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