Stem cells have the ability to develop into many different types of cells. One healthy stem cell can grow and develop into a group of liver cells or blood cells or nerve cells -- just about any specialized cell in the body. Genetic mistakes can create abnormal stem cells. An abnormal stem cell can develop into a group of abnormal cells, such as breast cancer cells, which can then grow and spread.
The study reviewed here found that HER2-positive breast cancers seem to have a large number of abnormal, cancerous stem cells. These cancerous stem cells appear to make HER2-positive breast cancers grow and spread. The researchers found a much lower number of cancerous stem cells in HER2-negative breast cancers.
HER2-positive breast cancers have extra HER2 genes and make too many HER2 protein receptors. About 1 out of every 4 breast cancers is HER2-positive. HER2-positive breast cancers tend to be more aggressive than HER2-negative breast cancers. This study suggests that cancerous stem cells may be the reason why HER2-positive breast cancers are more aggressive. The researchers think that the extra HER2 genes and proteins help abnormal stem cells develop.
Herceptin (chemical name: trastuzumab) is a targeted therapy medicine used to treat HER2-positive breast cancers. This study found that Herceptin lowered the number of abnormal stem cells in HER2-positive breast cancers by 80%. The researchers think that Herceptin works by targeting abnormal stem cells.
While this research won't have an immediate effect on treatment, it helps doctors better understand how breast cancers develop and spread and may lead to even better ways to treat breast cancer. Stay tuned to Breastcancer.org for the latest news on research to prevent, diagnose, and treat breast cancer.
ANN ARBOR, Mich., July 14 (MedPage Today) -- Malignant stem cells appear to fuel the growth and spread of aggressive HER2-positive breast cancer, suggesting clues for new therapeutic strategies, investigators here reported.
Breast cancer cells that overexpressed HER2 had four to five times as many cancer stem cells compared with HER2-negative breast cancer cells, Hasan Korkaya, Ph.D., of the University of Michigan, and colleagues reported online in Oncogene.
Moreover, when HER2-positive cells were implanted in mice, cancer stem cells led the invasion into surrounding tissue.
Treatment with trastuzumab (Herceptin) reduced the stem-cell population in HER2-positive breast cancer cells by 80%, suggesting the agent works by targeting the malignant stem cells.
"These studies provide support for the cancer stem cell hypothesis by suggesting that the effects of HER2 amplification on carcinogenesis, tumorigenesis and invasion may be due to its effects on normal and malignant mammary stem/progenitor cells," the authors said.
"Furthermore, the clinical efficacy of trastuzumab may relate to its ability to target the cancer stem cell population in HER2-amplified tumors."
A growing body of evidence suggests that many types of cancer, including breast cancer, may be driven by a small subset of tumor-initiating cells or cancer stem cells that exhibit stem cell-like properties. Several research groups have shown that cancer stem cells constitute 1% to 5% of the primary tumor, can form tumors in immunocompromised mice, and generate the phenotypic heterogeneity of the initial tumor.
The Michigan group also has shown that the stem-cell population in normal and malignant breast tissue exhibits increased expression of the enzyme aldehyde dehydrogenase as assessed by the Aldefluor assay. The investigators continued the research in the current study, which focused on the effects of HER2 overexpression on normal and malignant breast stem cells.
The experiments showed that HER2 exerts its effects on breast cancer via the cancer stem cells. Dr. Korkaya and colleagues reported that HER2 overexpression:
However, the PI3-K inhibitor LY294002 reduced the Aldefluor-positive population in both trastuzumab-sensitive and -resistant cell lines.
"These studies indicate that HER2 signaling regulates the mammary stem-progenitor cell population driving carcinogenesis and tumor invasion," the authors concluded.
The study was supported by the National Institutes of Health and the University of Michigan Cancer Center.
The authors reported no disclosures.
Primary source: Oncogene Source reference: Korkaya H et al. "HER2 regulates the mammary stem/progenitor cell population driving tumorigenesis and invasion." Oncogene. 2008;doi:10.1038/onc.2008.207.
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