Distinct organ-specific metastatic potential of individual breast cancer cells and primary tumors Journal Article
| Authors: | Minn, A. J.; Kang, Y.; Serganova, I.; Gupta, G. P.; Giri, D. D.; Doubrovin, M.; Ponomarev, V.; Gerald, W. L.; Blasberg, R.; Massague, J. |
| Article Title: | Distinct organ-specific metastatic potential of individual breast cancer cells and primary tumors |
| Abstract: | 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. |
| Keywords: | immunohistochemistry; controlled study; survival rate; human cell; genetics; mortality; nonhuman; bone metastasis; mouse; phenotype; animal; animals; mice; animal tissue; metastasis; breast cancer; gene expression; gene expression profiling; fluorescence; animal experiment; animal model; pathology; cell line, tumor; breast neoplasms; mice, inbred balb c; cancer invasion; gene expression regulation; lung metastasis; gene expression regulation, neoplastic; bagg albino mouse; oligonucleotide array sequence analysis; breast tumor; tumor cell line; neoplasm metastasis; organ specificity; progeny; antibody specificity; pleura effusion; neoplasm invasiveness; dna microarray; neoplasm transplantation; immune deficiency; transcriptome; bioluminescence; adrenal metastasis; cancer transplantation |
| Journal Title: | Journal of Clinical Investigation |
| Volume: | 115 |
| Issue: | 1 |
| ISSN: | 0021-9738 |
| Publisher: | American Society for Clinical Investigation |
| Date Published: | 2005-01-01 |
| Start Page: | 44 |
| End Page: | 55 |
| Language: | English |
| DOI: | 10.1172/jci22320 |
| PUBMED: | 15630443 |
| PROVIDER: | scopus |
| PMCID: | PMC539194 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 268" - "Export Date: 24 October 2012" - "CODEN: JCINA" - "Source: Scopus" |
