Research ArticleCancer

The Identification and Characterization of Breast Cancer CTCs Competent for Brain Metastasis

Science Translational Medicine  10 Apr 2013:
Vol. 5, Issue 180, pp. 180ra48
DOI: 10.1126/scitranslmed.3005109

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Cancer Cells in Blood, Directed to the Brain

Circulating tumor cells (CTCs) have been touted as exciting sources of diagnostic information, where the number of CTCs may correlate with disease progression or treatment success. However, little is known about the biology of these cells and why they are in the bloodstream, mostly because technology has prevented their long-term culture and analysis outside the body. Now, Zhang et al. have figured out how to isolate CTCs from breast cancer patients and study their metastatic potential.

Starting with cancer-associated circulating cells isolated from eight patients, the authors ultimately selected a population of CTCs from three patients that was EGFR+/HPSE+/ALDH1+/CD45/EpCAM. These CTCs were then grown as cell lines in culture, which allowed the authors to study their cancerous behavior in more detail. Zhang et al. hypothesized that a specific protein signature was present in these cells, essentially “telling” these cells to metastasize to the brain. After identifying the “brain metastasis selected markers (BMSMs)” as HER2+/EGFR+/HPSE+/Notch1+, the authors injected these selected patient CTCs into mice. By 6 weeks, between 60 and 80% of the BMSM CTCs metastasized to brain compared with only 0 to 20% for the parental CTC lines.

This protein signature, derived from human cells and tested in mice, could possibly govern brain metastatic breast cancer in patients. The next step will be to validate the presence of this BMSM CTC signature in a large number of breast cancer patients with brain metastases, with the goal of not only predicting disease course but also better understanding metastatic cancer.