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Tuesday, May 18, 2010
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Scientists Identify Markers on Human Breast Cancer Cells Linked to Development of an Aggressive, But Less Common Form of Breast Cancer

Scientists have identified a group of surface markers on cells linked to an aggressive type of breast cancer called estrogen receptor-negative cancer. In this preliminary study, estrogen-negative breast cancer developed when three markers, CD44+, CD49fhi, and CD133hi were present simultaneously on the surface of human cells taken from breast cancer patients and transplanted into a mouse; this is called a xenograft model. The scientists named these human cells with tumor-forming ability in mice, xenograft-initiating cells, or XIC. The research, conducted by scientists at the National Cancer Institute (NCI), part of the National Institutes of Health, appeared online May 18, 2010, and in print June 1, 2010, in Cancer Research.

Surface markers, usually proteins, are visualized on many cell types using antibodies or other detection methods. To identify surface markers of estrogen receptor-negative breast cancer stem-like cells, the investigators tested different populations of human breast cancer cells for their ability to form tumors when injected into the fat pads of the mammary glands of mice with compromised immune systems. The various tumor cell populations were prepared by a technique called flow cytometry, in which distinct antibodies bind to specific cell surface markers, resulting in separate subpopulations of cells.

The identification of specific markers on cells that are associated with estrogen receptor-negative breast cancer is important because this type of breast cancer is more difficult to treat than estrogen receptor-positive breast cancer. Estrogen receptor-positive breast cancers may be treated with medications such as tamoxifen, which interfere with the activity of estrogen. But no targeted therapies are yet available for patients with estrogen receptor-negative breast tumors. These cancers are currently treated with chemotherapy drugs that are toxic to many cells, not just cancer cells, and which can be hard for patients to tolerate.

"We are excited but cautious at the prospect that the presence of the XIC markers on estrogen receptor-negative breast cancer cells may present a selective target for early detection imaging and for personalized therapy," said Barbara K. Vonderhaar, Ph.D., NCI scientist emeritus of the Mammary Biology and Tumorigenesis Laboratory, Center for Cancer Research.

Although tumors from only four patients were evaluated, XIC with the same marker combination was identified in all cases. These limited data provide a basis to expand this work, said Vonderhaar. In addition, it may be important to determine if this XIC marker combination applies to estrogen receptor-positive breast cancer cells as well.

The scientists also demonstrated, for the first time, that the common markers CD44+, CD24- on the surface of stem cells were not necessarily or exclusively associated with growth in tumors of estrogen receptor-negative breast cancer. The identification of XIC may encourage investigators to re-evaluate the merits of therapeutically targeting CD44+, CD24-.

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For more information on NCIís Mammary Biology and Tumorigenesis Laboratory, visit: http://ccr.cancer.gov/labs/lab.asp?labid=141

Reference:
M J Meyer, et al. CD44+ CD49fhi CD133hi Defines Xenograft-Initiating Cells in Estrogen Receptor Negative Breast Cancer. Cancer Research, June 1, 2010. DOI: 10.1158/0008-5472.CAN-09-3619.

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