Biomarkers Found for Metastatic Breast Tumor Cells

Some breast tumor circulating cells in the bloodstream are marked by a constellation of biomarkers that identify them as those destined to metastasize in the brain.

Sophisticated techniques have been used to test samples of circulating breast tumor cells to identify and characterize the biomarkers that are the signature of the cells destined to seed the brain with a deadly spread of cancer.

Scientists at Baylor College of Medicine (Houston, TX, USA) collected blood samples from 38 patients with metastatic or nonmetastatic breast cancer. Isolated peripheral blood mononuclear cells (PBMCs) were separated, analyzed, and sorted with the BD FACSAria II 3Laser high-speed sorting flowcytometer (Becton Dickinson; Franklin Lakes, NJ, USA). The circulating tumor cells were cultured and injected into animals. Total ribonucleic acid (RNA) from the PBMCs was amplified by real time polymerase chain reaction.

The biomarkers identified by the scientists included human epidermal growth factor receptor 2 (HER2+), epidermal growth factor receptor (EGFR), heparanase (HPSE) and Notch1, a single-pass transmembrane receptor. Together, these four proteins, previously known to be associated with cancer metastasis, spell out the signature of circulating tumors cells that travel to the brain. The scientists did not find evidence of the epithelial cell adhesion molecule (EpCAM). The study not only identifies a novel signature of circulating tumor cells, it shows the limitations of currently approved platforms used to identify cancer in this way. Analyzing such cells can help scientist understand how the disease spreads, which may be an initial step in developing new methods of treating metastatic disease.

Dario Marchetti, PhD, professor of pathology and lead author said, "We don't claim that these biomarkers are the only important ones. We hope to find novel markers in brain metastasis that will make diagnosis and monitoring even more targeted." The investigators are also trying to find ways to link these circulating tumor cells back to the signature of the original or primary tumor. The study was published on April 10, 2013, in the journal Science Translational Medicine.

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