Gene expression profile of breast cancer cell line MDA-MB-231 xenograft - discovery set

Progression to stage IV disease remains the main cause of breast cancer-related deaths. Increasing knowledge of the hematogenous phase of metastasis is key for exploiting the entire window of opportunity to interfere with early dissemination and to achieve a more effective disease control. On the hypothesis that the distinguishing molecular features of circulating tumor cells (CTCs) reveal useful information on metastasis biology and disease outcome, we compared the transcriptomes of CTCs and solid primary/secondary lesions of the MDA-MB-231 xenograft model and provided evidence that blood-borne dissemination is regulated by numerous genes. Our new CTC-specific signature improved CTC detection and outcome prognostication in early-stage breast cancer patients compared to conventional CTC markers, and shed light on the metastatic process by highlighting the role of two genes. We injected MDA-MB-231 breast cancer cells in the mammary fat pad of NOD scid female mice and ran two independent gene expression profile experiments using tissues from three animals each. Sample profiling was carried out through the Whole-Genome DASL HT Assay. We first demonstrated that query oligos detect human and not murine RNA sequences, and compared the transcriptomes of (i) frozen sections of primary tumor nodules, lymph-nodes and lungs (solid lesions), (ii) circulating tumor cells isolated from blood samples (CTC), (iii) tumor cells disseminated to bone marrow flushed out from femur bones (DTC), and (iv) in vitro cultured MDA-MB-231 cells (parental cell line). A universal Mouse RNA reference was used as negative control (CG96_UMR).