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August 28, 2006

Diverse pre-cancerous cells can cooperate to produce cancer

ANN ARBOR, MI – If two nearby pre-cancerous cells work together, they have a better chance of surviving and becoming cancer, according to a new University of Michigan theory.

A diverse collection of tumor cells can sometimes overcome a body’s natural defenses more effectively than any one type alone, said Robert Axelrod, a professor at the U-M Gerald R. Ford School of Public Policy and the Department of Political Science.

Robert AxelrodAxelrod and his colleagues were inspired by “game theory” which is a perspective widely used in the social sciences to study the results of interaction between diverse individuals. Their analysis regarding how pre-cancerous cells cooperate with each other raises new questions about how different treatments succeed or fail.

“This analysis does not replace the existing view of cancer as the expansion of one initial cell, but rather this is an additional way of thinking of how cancer develops over time,” said Axelrod, the paper’s lead author.

For cancer to develop, a series of mutations must occur in a cell’s genetic structure. The researchers hypothesize that individual cells do not need to accumulate every trait of a cancer cell to develop into a cancer cell. Instead, neighboring cells actually share their resources. Some tumor cells may provide limited resources that other cells require, allowing for the survival of more cells, which in turn allows mutations to accumulate more quickly.

For example, cancer cells produce certain types of growth factors. One cell may produce one type of growth factor while a nearby cell produces a different type of growth factor. The two cells share both growth factors, feeding each other as well as other neighboring cells. In another example, the first cell to promote the growth of new blood vessels needed to feed the tumor benefits all the other nearby pre-cancerous cells. Both processes eventually lead to development of cancer.

Kenneth Pienta"What we're suggesting is that not all cancer cells are created equally, especially early cells that are trying to establish themselves. If you can identify the factors supporting the cells that have not made the complete transition to a full-fledged cancer cell, we can stop those cells from developing. That could potentially become one way to treat the cancer," said Dr. Kenneth Pienta, professor of internal medicine at the U-M Medical School and director of Urologic Oncology at the U-M Comprehensive Cancer Center.

Pienta is the paper’s co-author, as well as David Axelrod of the Department of Genetics and Cancer Institute of New Jersey at Rutgers – The State University of New Jersey.

The analysis appears the week of Aug. 28 in the early online edition of Proceedings of the National Academy of Sciences.

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