Distinct organ-specific metastatic potential of individual breast cancer cells and primary tumors.
We used bioluminescence imaging to reveal patterns of metastasis formation by human breast cancer cells in immunodeficient mice. Individual cells from a population established in culture from the pleural effusion of a breast cancer patient showed distinct patterns of organ-specific metastasis. Single-cell progenies derived from this population exhibited markedly different abilities to metastasize to the bone, lung, or adrenal medulla, which suggests that metastases to different organs have different requirements. Transcriptomic profiling revealed that these different single-cell progenies similarly express a previously described "poor-prognosis" gene expression signature. Unsupervised classification using the transcriptomic data set supported the hypothesis that organ-specific metastasis by breast cancer cells is controlled by metastasis-specific genes that are separate from a general poor-prognosis gene expression signature. Furthermore, by using a gene expression signature associated with the ability of these cells to metastasize to bone, we were able to distinguish primary breast carcinomas that preferentially metastasized to bone from those that preferentially metastasized elsewhere. These results suggest that the bone-specific metastatic phenotypes and gene expression signature identified in a mouse model may be clinically relevant.
Minn
Andy J
AJ
Cancer Biology and Genetics Program, Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Kang
Yibin
Y
Serganova
Inna
I
Gupta
Gaorav P
GP
Giri
Dilip D
DD
Doubrovin
Mikhail
M
Ponomarev
Vladimir
V
Gerald
William L
WL
Blasberg
Ronald
R
Massagué
Joan
J
D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D045744:Cell Line, Tumor; D005453:Fluorescence; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D009362:Neoplasm Metastasis / Q000235:genetics / Q000473:pathology*; D009368:Neoplasm Transplantation; D020411:Oligonucleotide Array Sequence Analysis; D009928:Organ Specificity; D010641:Phenotype; D011379:Prognosis; D015996:Survival Rate