The Isolation and Characterization of Brain Metastasis – Competent Breast Cancer CTCs

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SELECTBIO

Mechanisms of fatal brain metastatic breast cancer (BMBC) are largely unknown. Similarly, properties and biomarker identification of circulating tumor cells (CTCs), the “seeds” of metastasis, remain elusive. Here we report novel strategies investigating CTCs isolated from peripheral blood mononuclear cells (PBMCs) of patients with BMBC, including the development and characterization of CTC lines. We identified a unique BMBC CTC signature (HER2+/EGFR+/HPSE+/Notch1+/EpCAM-) by investigating CTCs that could not be captured by the FDA-approved Veridex CellSearchTM platform (EpCAM - negative CTCs). Second, we analyzed the invasive and metastatic competencies of isolated CTCs. Established CTC lines over-expressing the BMBC signature were highly invasive and capable to form brain metastasis in xenografts. Third, tumor cell morphologies of CTC - induced metastases closely resembled those of pathologically assessed tumors of patients whose blood was source of isolated CTCs. Fourth, the expression of proteins of the BMBC signature was detected in CTC - induced BMBC. Collectively, we provide first-time evidence of human CTCs isolation and long-term growth, the establishment of CTC lines, and CTC metastatic competency in the presence of a biomarker signature necessary to promote BMBC.