Abstract
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 PGE2 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-μm 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.
Original language | English (US) |
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Pages (from-to) | 267-275 |
Number of pages | 9 |
Journal | Journal of Surgical Research |
Volume | 131 |
Issue number | 2 |
DOIs | |
State | Published - Apr 2006 |
Keywords
- Bone metastasis
- Breast cancer
- COX-2
- IL-11
ASJC Scopus subject areas
- Surgery