Link Between Inflammation and Breast Cancer Metastases Identified ...

• Metastases increased in mice with breast cancer and arthritis.
• Mast cells one of the major underlying causes of metastases.
• Therapies could be developed to decrease metastases.

CHICAGO ? The incidence of breast cancer-associated metastasis was increased in animal models of the chronic inflammatory condition arthritis, according to results of a preclinical study presented at the AACR Annual Meeting 2012, held here March 31 ? April 4. The results indicate that inflammatory cells known as mast cells play a key role in this increase and that interfering with mast cells reduces the occurrence of bone and lung metastases.

??The most devastating aspect of breast cancer is the emergence of tumor cells that grow to distant organs,? said Lopamudra Das Roy, Ph.D., research assistant professor at the University of North Carolina at Charlotte, N.C. ?It has been reported that sites of chronic inflammation are associated with the establishment and growth of tumor cells.?

Prior research conducted by Das Roy established that the incidence of breast cancer metastasis to the bone and lungs was increased in arthritic mice. Because both breast cancer and arthritis are prevalent in women, specifically postmenopausal women, the researchers conducted an additional study using two groups of mice to identify what might be causing the association between arthritis and breast cancer metastases.

The first group of mice had spontaneous arthritis and was induced to have breast cancer. The second group of mice had spontaneous breast cancer and was induced to have arthritis. Because mice in both groups had enhanced numbers of mast cells within the bone and lung, Das Roy and colleagues focused on understanding how these cells might influence breast cancer metastasis.

?We found that there were many proinflammatory factors that are upregulated in the arthritic microenvironment and several of these proinflammatory factors known to influence metastases are produced by mast cells, which are activated by tumor-derived stem cell factor (SCF) binding to its receptor c-Kit,? Das Roy said.

A subsequent key finding was that SCF/c-Kit signaling was increased in arthritic mice with breast cancer versus nonarthritic mice with breast cancer. This set the stage for examining the effects of blocking this signaling.

When the mice were treated with a therapy to target the c-Kit mast cell receptor in combination with celecoxib (a drug used to treat autoimmune arthritis), the incidence of breast cancer metastasis to the bone and lung was greatly reduced.

?The clinical implications of this research are huge,? Das Roy said. ?We already have data that show that women with breast cancer and arthritis have lower survival as compared with women with breast cancer and no arthritis. This research indicates that we may be able to design a therapy to block SCF/c-Kit signaling, which could help reduce metastases to the bone and lungs.?

This research was funded by a postdoctoral grant on behalf of the Fiscal Year 2008 Department of Defense Breast Cancer Research Program.

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About the AACR

Founded in 1907, the American Association for Cancer Research (AACR) is the world?s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR?s membership includes 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 18,000 attendees. In addition, the AACR publishes seven peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the Scientific Partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of individual and team science grants in cancer research that have the potential for patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. ?

For more information about the AACR, visit www.AACR.org.

Media Contact:
Jeremy Moore
(215) 446-7109
Jeremy.Moore@aacr.org
In Chicago, March 31 ? April 4:
(312) 528-8206???

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