Bone metastasis from breast cancer involves elevated IL-11 expression and the gp130/STAT3 pathway
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To evaluate the relationship between IL-11 and bone metastasis in patients with breast cancer and explore the potential molecular mechanism, total serum samples were collected from 180 breast cancer patients and 20 women without breast cancer. The serum expression level of interleukin (IL)-11, connective tissue growth factor (CTGF), transforming growth factor-β, and Tracp5b was determined by enzyme-linked immunosorbent assay, and mRNA expression of IL-11 in fresh breast cancer tissue was determined by RT-PCR. Immunohistochemical staining was used to detect the expression of IL-11 and CTGF in breast cancer tissue, and Western blot was used to detect the expression of p-38, p-C-JUN, p-STAT3, and p-gp130 in fresh breast cancer tissue. DNA-binding activity of AP-1 was examined by electrophoretic mobility shift assay. Differences were statistically analyzed between the group with breast cancer metastatic to bone (MBC-B) and the group with only primary breast cancer (PBC). Serum level and mRNA expression of IL-11 in the MBC-B group were significantly higher than those in the PBC group. IL-11 immunohistochemical staining showed that the percentage of positively stained cells in the MBC-B group (57.5 %) was significantly higher than that in the PBC group (14.29 %). Western blot analysis showed higher expression of p-p38, p-C-JUN, p-STAT3, and p-gp130 in the MBC-B group than in the PBC group. DNA-binding activity of AP-1 was significantly higher in the MBC-B group than in the PBC group. These data suggest that IL-11 is associated with bone metastasis and may be of value for predicting bone metastasis from breast cancer.
KeywordsBreast cancer Bone metastasis Interleukin-11 gp130 STAT3
Breast cancer metastatic to bone
Primary breast cancer
Transforming growth factor-β
Connective tissue growth factor
This work was supported by the National Science Foundation of China (81071631), Tianjin Medical University Science Foundation (2010KY36), Key Project of Natural Science Foundation of Anhui Education Department (KJ2010A179). We also thank Dr. Zhuang Cui for his professional statistical suggestions.
Conflict of interest
The authors declare that they have no competing interests.
- 2.Bohn OL, Nasir I, Brufsky A, Tseng GC, Bhargava R, MacManus K, Chivukula M. Biomarker profile in breast carcinomas presenting with bone metastasis. International J Clin Exp Pathol. 2009;3(2):139–46.Google Scholar
- 10.Ehata S, Hanyu A, Fujime M, Katsuno Y, Fukunaga E, Goto K, Ishikawa Y, Nomura K, Yokoo H, Shimizu T, et al. Ki26894, a novel transforming growth factor-beta type I receptor kinase inhibitor, inhibits in vitro invasion and in vivo bone metastasis of a human breast cancer cell line. Cancer Sci. 2007;98(1):127–33.PubMedCrossRefGoogle Scholar
- 13.Kakonen SM, Selander KS, Chirgwin JM, Yin JJ, Burns S, Rankin WA, Grubbs BG, Dallas M, Cui Y, Guise TA. Transforming growth factor-beta stimulates parathyroid hormone-related protein and osteolytic metastases via Smad and mitogen-activated protein kinase signaling pathways. The J Biol Chem. 2002;277(27):24571–8.CrossRefGoogle Scholar
- 21.Paul SR, Bennett F, Calvetti JA, Kelleher K, Wood CR, O’Hara RM Jr, Leary AC, Sibley B, Clark SC, Williams DA, et al. Molecular cloning of a cDNA encoding interleukin 11, a stromal cell-derived lymphopoietic and hematopoietic cytokine. Proc Natl Acad Sci USA. 1990;87(19):7512–6.PubMedCrossRefGoogle Scholar