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Jefferson researchers show antibody to breast cancer-secreted protein blocks metastasis
Date:7/8/2008

(PHILADELPHIA) Scientists at the Kimmel Cancer Center at Thomas Jefferson University in Philadelphia have made a key discovery about the mechanism of breast cancer metastasis, the process by which cancer spreads. Focusing on a gene dubbed "Dachshund," or DACH1, they are beginning to pinpoint new therapeutic targets to halt the spread of cancer.

Reporting their findings in the Proceedings of the National Academy of Sciences, researchers led by Richard Pestell, M.D., Ph.D., director of the Kimmel Cancer Center at Jefferson and professor and chair of Cancer Biology at Jefferson Medical College, showed that breast cancer cells secrete a common inflammatory protein, IL-8. When the scientists blocked the protein in mice with an antibody, they found that it completely halted the spread of breast cancer to the lungs.

In addition, the team found that the DACH1 gene normally blocks the production of IL-8.

DACH1 is frequently lost or inactive in invasive breast cancer and can prevent the migration and invasion of breast cancer cells. The finding suggests that IL-8 is a potential target for new therapies to block breast cancer spread.

"This is a very important study by Dr. Pestell and his colleagues that demonstrates that the protein dachshund blocks metastasis in a mouse model and that this occurs through reduced production of the chemokine IL-8," says Max Wicha, M.D., director of the University of Michigan Comprehensive Cancer Center in Ann Arbor. "Interestingly reduced dachshund and increased IL-8 are associated with aggressive metastatic breast cancer in women. Our laboratory has found that IL-8 regulates breast cancer stem cells and that these cells mediate metastasis. Dr Pestell's work suggests that dachshund is a key regulator of this process."

DACH1 normally regulates eye development and development of other tissues, playing a role in determining the fate of some types of cells. In previous work, Dr. Pestell
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Contact: Steve Benowitz
steven.benowitz@jefferson.edu
215-955-5291
Thomas Jefferson University
Source:Eurekalert

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