A multigenic program mediating breast cancer metastasis to bone

Cancer Cell. 2003 Jun;3(6):537-49. doi: 10.1016/s1535-6108(03)00132-6.


We investigated the molecular basis for osteolytic bone metastasis by selecting human breast cancer cell line subpopulations with elevated metastatic activity and functionally validating genes that are overexpressed in these cells. These genes act cooperatively to cause osteolytic metastasis, and most of them encode secreted and cell surface proteins. Two of these genes, interleukin-11 and CTGF, encode osteolytic and angiogenic factors whose expression is further increased by the prometastatic cytokine TGF beta. Overexpression of this bone metastasis gene set is superimposed on a poor-prognosis gene expression signature already present in the parental breast cancer population, suggesting that metastasis requires a set of functions beyond those underlying the emergence of the primary tumor.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bone Neoplasms / genetics*
  • Bone Neoplasms / secondary*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology*
  • Chromatin / metabolism
  • Connective Tissue Growth Factor
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immediate-Early Proteins / genetics*
  • Insulin-Like Growth Factor Binding Proteins / metabolism
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Interleukin-11 / genetics*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Mitogens / metabolism
  • Neoplasm Invasiveness
  • Neoplasm Proteins / analysis
  • Nucleic Acid Hybridization
  • Oligonucleotide Array Sequence Analysis
  • Osteolysis / pathology
  • Precipitin Tests
  • Transforming Growth Factor beta / genetics
  • Tumor Cells, Cultured


  • CCN2 protein, human
  • CCN2 protein, mouse
  • Chromatin
  • Immediate-Early Proteins
  • Insulin-Like Growth Factor Binding Proteins
  • Intercellular Signaling Peptides and Proteins
  • Interleukin-11
  • Mitogens
  • Neoplasm Proteins
  • Transforming Growth Factor beta
  • Connective Tissue Growth Factor