Abstract
Bone is a major target for metastases in the most frequent solid tumors, which result in severe complications and are a major cause of pain. A bone metastasis gene expression signature was identified using human breast cancer cells in a mouse model. The bone metastasis-related genes encode secretory and cell surface proteins implicated in bone-homing (CXCR4), angiogenesis (CTGF and FGF5), invasion (MMP-1 and ADAMTS1), and osteoclast recruitment (IL11). This signature superimposes on the 70-gene poor prognosis gene expression signature for breast cancer, and only ADAMTS1, CTGF and IL11 were found to be overexpressed in human primary breast cancers with bone relapse. We analyzed the expression of the six bone metastasis-related genes in bone metastases from patients with different types of solid tumors, to assess its relevance in human clinical samples. MMP-1, CXCR4, FGF5 and CTGF were found to be overexpressed in tumor cells of human bone metastases when compared to a human normal epithelial cell line. All the analyzed genes were overexpressed in the tumor cells of breast cancer bone metastases when compared to normal breast tissue. We did not detect any differences between the expression of these genes in bone metastases from breast cancer or from other types of solid tumors. Importantly, there was a significant correlation between the expressions of IL11/CTGF, IL11/ADAMTS1, CTGF/CXCR4, CTGF/ADAMTS1, and MMP-1/ADAMTS1, supporting the cooperative function of these proteins in the bone microenvironment, and the potential functional role of these genes in the establishment of bone metastases in vivo.
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Abbreviations
- BM:
-
Bone metastasis
- SREs:
-
Skeletal-related events
- BC:
-
Breast cancer
- OST:
-
Other solid tumors
- RT:
-
Radiation therapy
- NBT:
-
Normal breast tissue
- LMPC:
-
Laser microdissection and pressure catapulting
References
Kang Y et al (2003) A multigenic program mediating breast cancer metastasis to bone. Cancer Cell 3(6):537–549
Van’t Veer LJ et al (2002) Gene expression profiling predicts clinical outcome of breast cancer. Nature 415(6871):530–536
Smid M et al (2006) Genes associated with breast cancer metastatic to bone. J Clin Oncol 24(15):2261–2267
Minn AJ et al (2005) Distinct organ-specific metastatic potential of individual breast cancer cells and primary tumors. J Clin Invest 115(1):44–55
Minn AJ et al (2005) Genes that mediate breast cancer metastasis to lung. Nature 436(7050):518–524
Landemaine T et al (2008) A six-gene signature predicting breast cancer lung metastasis. Cancer Res 68(15):6092–6099
Klein A et al (2009) Identification of brain- and bone-specific breast cancer metastasis genes. Cancer Lett 276(2):212–220
Bos PD et al (2009) Genes that mediate breast cancer metastasis to the brain. Nature 459(7249):1005–1009
Schroeder A et al (2006) The RIN: an RNA integrity number for assigning integrity values to RNA measurements. BMC Mol Biol 7:3
Lu X et al (2009) ADAMTS1 and MMP1 proteolytically engage EGF-like ligands in an osteolytic signaling cascade for bone metastasis. Genes Dev 23(16):1882–1894
Cailleau R et al (1974) Breast tumor cell lines from pleural effusions. J Natl Cancer Inst 53(3):661–674
Paget S (1889) The distribution of secondary growths in cancer of the breast. Lancet 133:3
Bernards R, Weinberg RA (2002) A progression puzzle. Nature 418(6900):823
Acknowledgments
Authors want to acknowledge the Terry Fox Foundation and the Liga Portuguesa Contra o Cancro (NRS) for funding. S. Casimiro is supported by a Post-Doctoral Fellowship from FCT (SFRH/BPD/34801/2007).
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Casimiro, S., Luis, I., Fernandes, A. et al. Analysis of a bone metastasis gene expression signature in patients with bone metastasis from solid tumors. Clin Exp Metastasis 29, 155–164 (2012). https://doi.org/10.1007/s10585-011-9438-0
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DOI: https://doi.org/10.1007/s10585-011-9438-0