COX-2 involvement in breast cancer metastasis to bone

Oncogene. 2007 May 31;26(26):3789-96. doi: 10.1038/sj.onc.1210154. Epub 2007 Jan 8.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Blotting, Western
  • Bone Neoplasms / secondary*
  • Cell Line, Tumor
  • Cyclooxygenase 2 / drug effects
  • Cyclooxygenase 2 / metabolism*
  • Cyclooxygenase 2 Inhibitors / pharmacology
  • Dinoprostone / biosynthesis
  • Female
  • Humans
  • Mammary Neoplasms, Experimental / enzymology*
  • Mammary Neoplasms, Experimental / pathology*
  • Mice
  • Neoplasm Metastasis / prevention & control*
  • Transfection


  • Cyclooxygenase 2 Inhibitors
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2
  • Dinoprostone