A multigenic program mediating breast cancer metastasis to bone.
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.
Kang
Yibin
Y
Cell Biology Program and Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
Siegel
Peter M
PM
Shu
Weiping
W
Drobnjak
Maria
M
Kakonen
Sanna M
SM
Cordón-Cardo
Carlos
C
Guise
Theresa A
TA
Massagué
Joan
J
D000818:Animals; D001859:Bone Neoplasms / Q000235:genetics* / Q000556:secondary*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D002843:Chromatin / Q000378:metabolism; D055513:Connective Tissue Growth Factor; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics*; D018969:Insulin-Like Growth Factor Binding Proteins / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D017370:Interleukin-11 / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008934:Mitogens / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000032:analysis; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D010014:Osteolysis / Q000473:pathology; D011233:Precipitin Tests; D016212:Transforming Growth Factor beta / Q000235:genetics; D014407:Tumor Cells, Cultured
C526317:CCN2 protein, human; C526318:CCN2 protein, mouse; D002843:Chromatin; D017874:Immediate-Early Proteins; D018969:Insulin-Like Growth Factor Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; D017370:Interleukin-11; D008934:Mitogens; D009363:Neoplasm Proteins; D016212:Transforming Growth Factor beta; D055513:Connective Tissue Growth Factor