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Shape Changing Fat Cells Cause Rapid Breast Cancer Growth

A latest study conducted by researchers at UT Southwestern has revealed that fat cells, or adipocytes, which grow very close to breast cancer cells, can change into other cell types, which lead to tumor growth. The findings can help in finding new method of fighting breast cancer, a disease affecting more than 300,000 women in U.S each year and kills nearly 45,000 annually.

Study leader Philipp Scherer, PhD, Professor of Internal Medicine and Cell Biology and a member of the Harold C. Simmons Comprehensive Cancer Center at UTSW, said, "We identified novel adipocyte-derived cell types in the mammary gland that offer a fertile soil for breast cancer tumor invasion and growth."

Obesity has for long been thought to be a risk factor for breast cancer and worse prognosis. Studies have shown that fat cells, which are in close contact with breast tumor cells can break down their lipids to give fuel for new tumor cells. However, Scherer said that it Is really unclear what different roles these adipocytes play in breast cancer progression.

To solve this puzzle, Qingzhang Zhu, PhD, an Instructor of Internal Medicine and member of the Scherer laboratory, and his colleagues used a genetic technique that "painted" adipocytes in lab mice so they lit up a fluorescent color, making it possible to follow these cells long term. When the researchers implanted breast tumors in the mice or genetically manipulated the rodents' own breast cells to turn them into tumor cells, they saw that nearby fat cells shrank and took on forms different from basic adipocytes.

Genetic testing to identify which genes were active in these fat cells showed these cells first broke down to an earlier stage in development, then after that developed genetic markers of other cell types, including connective tissue cells, muscle cells, and immune cells.

More study revealed that these changed fat cells helped breast cancer tumors to grow. However, this property also depended critically on their ability to give energy to neighboring tumor cells. In addition, the properties of the cell types that fat cells morph into after they lose their lipids and their fat cell identity are important, since they add significantly to the local fibrosis, which contributes to the stiffness of breast tissue. When the researchers enhanced the lipid-storing capacity of mature fat cells, they ceased to morph into other cell types and no longer promoted tumor growth.

Dr Scherer concluded, "The mechanism for how adipocytes change into other cell types is not yet clear; however, a chemical signal from tumor cells is probably responsible for this phenomenon. He and his colleagues plan to search for this signal and look for other ways to manipulate this system to discourage breast cancer growth."

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