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.
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.
Tumor cells were labeled with a fluorescent marker and then introduced into the mouse’s circulation by tail vein injection. Subsequently, the lungs were excised, filled with agarose—a type of complex carbohydrate—to provide structural support, sliced, and placed in culture.
This allowed the researchers to follow the growth of the tumor cells over time, and to view growth from single cells to proliferating cell colonies. In each case the cells that were highly metastatic in mice were also highly metastatic in the PuMA. The same was true for low metastatic cells.
With this validation in place, the team showed that the assay also provided an opportunity to evaluate new cancer drugs for their specific effects on metastatic progression.
This is important because most cancer drugs in development screen for anti-cancer activity in primary tumor growth and not in metastasis.
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-.
This is important because most cancer drugs in development screen for anti-cancer activity in primary tumor growth and not in metastasis.
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-.
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.
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.
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.
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.
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