COX-2 involvement in breast cancer metastasis to bone.
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.
Singh
B
B
Department of Surgical Oncology and Advanced Research Center for Microscopic Disease, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Berry
J A
JA
Shoher
A
A
Ayers
G D
GD
Wei
C
C
Lucci
A
A
D000818:Animals; D015153:Blotting, Western; D001859:Bone Neoplasms / Q000556:secondary*; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000187:drug effects / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis; D005260:Female; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000201:enzymology* / Q000473:pathology*; D051379:Mice; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D014162:Transfection
D052246:Cyclooxygenase 2 Inhibitors; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D015232:Dinoprostone