Transcriptomics

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Towards understanding breast cancer mechanisms to metastasize


ABSTRACT: How organ-specific metastatic traits accumulate in primary tumors remains unknown. We identified a role of the primary tumor stroma in selecting breast cancer cells that are primed for metastasis in the bone. A fibroblast-rich stroma in breast tumors creates a microenvironment that is similar to that of bone metastases in its abundance of the cytokines CXCL12 and IGF1. Heterogeneous breast cancer cell populations growing in such mesenchymal environment evolve towards a preponderance of clones that thrive on CXCL12 and IGF1. Fibroblast-driven selection of bone metastatic clones in mammary tumors is suppressed by CXCL12 and IGF1 receptor inhibition. Thus, a fibroblast-rich stroma in breast tumors can pre-select bone metastatic seeds, promoting the evolution of metastatic traits and the interplay between a primary tumor and its distant metastases. Affymetrix U133 Plus2 arrays were hybridized according to the manufacturer's procedure using RNA extracted from 47 primary breast tumors. Specific gene sets were evaluated in this cohort.

OTHER RELATED OMICS DATASETS IN: E-GEOD-43306

ORGANISM(S): Homo sapiens  

SUBMITTER: John Foekens  Xiang H Zhang   Joan Massagué   Marcel Smid    

PROVIDER: E-GEOD-47389 | ArrayExpress | 2013-11-01

SECONDARY ACCESSION(S): GSE47389PRJNA205399

REPOSITORIES: GEO, ArrayExpress

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Publications

Selection of bone metastasis seeds by mesenchymal signals in the primary tumor stroma.

Zhang Xiang H-F XH   Jin Xin X   Malladi Srinivas S   Zou Yilong Y   Wen Yong H YH   Brogi Edi E   Smid Marcel M   Foekens John A JA   Massagué Joan J  

Cell 20130801 5


How organ-specific metastatic traits arise in primary tumors remains unknown. Here, we show a role of the breast tumor stroma in selecting cancer cells that are primed for metastasis in bone. Cancer-associated fibroblasts (CAFs) in triple-negative (TN) breast tumors skew heterogeneous cancer cell populations toward a predominance of clones that thrive on the CAF-derived factors CXCL12 and IGF1. Limiting concentrations of these factors select for cancer cells with high Src activity, a known clini  ...[more]

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