U-M researchers find indirect path to attack breast cancer stem cells

Bone marrow-derived cells create 'niche' to harbor cancer stem cells; New therapies could target the niche to kill the stem cells

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added 01/17/2011

Ann Arbor - Scientists at the University of Michigan Comprehensive Cancer Center have identified a potential new way of attacking breast cancer stem cells, the small number of cells in a tumor that fuel its growth and spread.

Researchers found that breast cancer stem cells are regulated by a type of cell derived from bone marrow, called mesenchymal stem cells. These cells are drawn from the bone marrow to the cancer and create a "niche" for the cancer stem cells, allowing them to replicate.

"The importance of this is that we may be able to attack breast cancer stem cells indirectly by blocking these signals from the niche," says study author Max S. Wicha, M.D.going to a new website, Distinguished Professor of Oncology and director of the University of Michigan Comprehensive Cancer Center.

Breast cancer stem cells were first identified by Wicha and colleagues at the University of Michigan in 2003. Cancer stem cells are believed to be resistant to current chemotherapies and radiation treatment, which researchers say may be the reason cancer so often returns after treatment.

Little is known about the cancer stem cell niche - a type of microenvironment that is highly associated with tumor growth and metastasis. The researchers looked at mesenchymal stem cells, which arise in bone marrow. They found that breast cancers in mice sent out signals which attracted mesenchymal stem cells from the bone marrow into the tumor where these cells interacted and stimulated the growth of breast cancer stem cells.

Researchers then identified two signals from a cytokine network - a type of protein that affects how cells communicate - that were responsible for stem cell regulation. These same cytokines play a role in inflammation and drugs that block them have already been approved for the treatment of inflammatory diseases such as rheumatoid arthritis. By blocking these cytokine signals, researchers hope that they can successfully target the cancer stem cell population providing a more effective treatment for breast cancer.

Results of the study appear in the Jan. 15 issue of Cancer Researchgoing to a new website.

Breast cancer statistics: 209,060 Americans will be diagnosed with breast cancer this year and 40,230 will die from the disease, according to the American Cancer Societygoing to a new website.

Additional authors: From U-M: Suling Liu, Sing J. Ou, Shawn Clouthier, Shivani H. Patel, Hasan Korkaya, Amber Heath, Julie Dutcher, Celina G. Kleer, Younghun Jung, Gabriela Dontu, Russell Taichman; from Centre de Recherche en Cancerologie de Marseille: Christophe Ginestier

Funding: National Institutes of Health, Taubman Research Institute.

Disclosure: Wicha has financial holdings in OncoMed Pharmaceuticals, which has applied for a patent on cancer stem cell technologies.

Reference: Cancer Research, Vol. 71, No. 2, Jan. 15, 2011going to a new website.

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Written by Nicole Fawcett

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