Anomalous Stem Cells Found in Breast Cancer Tumors

Human Epidermal Growth Factor Receptor 2 (HER2) positive stem cells have been found in HER2- negative breast cancer tumors.

The findings shed light on how the disease can evade treatment and could improve diagnosis because if a tumor contains HER2, an estrogen receptor protein, a progesterone receptor protein, or all three, or none, it can have an enormous impact on the tumor's aggressiveness, the patient's overall prognosis, and treatment choices.

Scientists at the University of California Davis (CA, USA) and their collaborators examined breast tumors previously thought to lack the HER2 protein, which, when overexpressed, is associated with disease recurrence. They also analyzed the stem cells for CD44 and CD24 cell surface proteins that indicate cancer aggressiveness and act as breast cancer stem cells (BCSC) markers. The HER2/CD44 feature was analyzed in 40 primary and recurrent breast cancer specimens. Tumor aggressiveness and radioresistance were analyzed by gap filling, Matrigel (BD Bioscience; San Jose, CA, USA) invasion, tumor-sphere formation, and clonogenic survival assays.

The team found that the HER2-positive, CD44 positive, CD24 negative/low BCSCs were more aggressive and highly resistant to radiotherapy. These characteristics were significantly reduced by Herceptin or short interfering ribonucleic acid (RNA). HER2 and CD44 positive BCSCs were found in 57.1% of primary tumors and 84.6% of recurrent tumors. In addition to identifying this previously hidden group of HER2-positive stem cells, further examination provided new insights into how these BCSCs maintain their resistance to treatment. A complex network of proteins, including HER2 and Signal transducer and activator of transcription 3 (STAT3), modulate metastasis, programmed cell death and other functions. As a result, these cells survive the gamut of traditional anticancer therapies.

Furthermore, this may open up new treatment options for HER2-negative patients and also provides a diagnostic pathway. Markers, such as CD44, could help clinicians identify aggressive, HER2-positive BCSCs in cancers that are ostensibly HER2-negative, individualizing treatment to match each patient's needs. These findings may also advance treatment for other cancers. Jian-Jian Li, MD, PhD, who led the study said, “This may open the possibility of treating HER2-positive stem cells in bone, lung, or brain cancers, which are all difficult to treat in the later stages." The study was published on the December 15, 2012, in the journal Clinical Cancer Research.

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University of California Davis
BD Bioscience