COX-2 induces IL-11 production in human breast cancer cells

J Surg Res. 2006 Apr;131(2):267-75. doi: 10.1016/j.jss.2005.11.582. Epub 2006 Feb 2.


Background: Cyclooxygenase-2 (COX-2) is overexpressed in 40% of human invasive breast cancers. Interleukin-11 (IL-11), a potent mediator of osteoclastogenesis, is involved in breast cancer metastasis to bone. Since breast cancers that overexpress COX-2 are associated with a higher rate of metastasis to bone, we hypothesized that COX-2 expression in tumor cells would induce IL-11.

Materials and methods: We transfected MCF-7 (poorly metastatic) and MDA-231 (highly metastatic) human breast cancer cell lines with COX-2 expression vectors. COX-2 overexpression was confirmed by Western blot and PGE(2) immunoassay, and IL-11 production was measured by immunoassay. We also used a nude mouse model to study COX-2 and IL-11 production from breast cancer cells that metastasized to bone. The bone-seeking clones (BSC) were isolated and cultured from the long bone metastases.

Results: COX-2 transfection caused an approximately 5- to 6-fold increase in IL-11 production in both MCF-7 and MDA-231 cells. MDA-435S-COX2-BSC (cells isolated from bone metastasis) produced elevated levels of IL-11 and PGE2 (an important mediator of COX-2) as compared to the parental MDA-435S-COX2 cells. Furthermore, a treatment with low 1- to 2-microm concentration NS-398 or Celecoxib significantly reduced the production of IL-11 in COX-2-transfected MDA-231 cells, thus confirming the involvement of COX-2 in IL-11 induction.

Conclusion: COX-2-mediated production of IL-11 in breast cancer cells may be vital to the development of osteolytic bone metastases in patients with breast cancer, and a COX-2 inhibitor may be useful in inhibiting this process.

MeSH terms

  • Animals
  • Blotting, Western
  • Bone Neoplasms / secondary
  • Breast Neoplasms / enzymology*
  • Breast Neoplasms / pathology*
  • Cyclooxygenase 2 / biosynthesis*
  • Cyclooxygenase 2 / physiology*
  • Female
  • Humans
  • Immunoassay
  • Interleukin-11 / biosynthesis*
  • Mice
  • Mice, Nude
  • Neoplasm Metastasis / physiopathology*
  • Transfection
  • Tumor Cells, Cultured
  • Up-Regulation


  • Interleukin-11
  • Cyclooxygenase 2