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Research points in new direction for cancer clues

Like a detective combing the scene of a crime for clues, researchers often target their search for cancer causes in the cells known as epithelial cells. After all, it is these cells that most often become cancerous, so it makes sense to look for what goes wrong inside these cells.

However, a new report from a team of Vanderbilt-Ingram Cancer Center scientists demonstrates that tumors can develop from completely normal epithelial cells solely because of changes in signals from nearby supporting cells.

Writing in the Feb. 6 issue of Science, the team reports the dramatic development of precancerous prostate lesions and invasive cancers in the forestomachs of mice bred to eliminate a particular cell signaling pathway only in fibroblasts. These fibroblasts are supporting cells adjacent to the epithelial cells.

"The key finding is that we were able to show that a signaling pathway in the fibroblasts is important and can have a dramatic effect on epithelial cells in these animals," said Dr. Harold L. Moses, Benjamin F. Byrd Professor of Oncology, director of the Vanderbilt-Ingram Cancer Center, and director of the Frances Williams Preston Laboratories of the T.J. Martell Foundation for Leukemia, Cancer and AIDS Research. The paper results from a collaboration between Moses' lab and the lab led by Dr. Eric G. Neilson, Hugh J. Morgan Professor and Chair of Medicine.

The Moses lab focuses on the role of transforming growth factor beta and its ability to either stimulate or inhibit cell growth depending upon the conditions. A standard approach to studying a particular protein or signaling pathway is to develop a genetically engineered "knock-out" mouse that does not express the particular protein in question. But TGF beta and its receptor are so critical to mammalian development, mice bred to eliminate this signaling pathway in all cells die as embryos.

To eliminate the TGF-beta pathway in only certain cells, the Moses lab in coll
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Contact: Cynthia Floyd Manley
cynthia.manley@vanderbilt.edu
615-936-5711
Vanderbilt University Medical Center
10-Feb-2004


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