COX-2 involvement in breast cancer metastasis to bone

B Singh, JA Berry, A Shoher, GD Ayers, C Wei, A Lucci - Oncogene, 2007 - nature.com
B Singh, JA Berry, A Shoher, GD Ayers, C Wei, A Lucci
Oncogene, 2007nature.com
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 …
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 E 2 (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.
nature.com