1. ¹Department of Surgical Oncology and Advanced Research Center for Microscopic Disease, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
2. ²Baylor College of Medicine, Houston, TX, USA
3. ³Department of Biostatistics & Applied Mathematics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Correspondence: Dr A Lucci, Department of Surgical Oncology, Unit 444, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. E-mail: alucci@mdanderson.org

⁴Current address: Johns Hopkins University School of Medicine, Baltimore, MD, USA.

⁵Current address: Department of Biostatistics, School of Medicine, Vanderbilt University, Nashville, TN, USA.

Received 25 May 2006; Revised 9 October 2006; Accepted 10 October 2006; Published online 8 January 2007.

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.