Fat cells, or adipocytes, that grow near breast cancer may shift to other cell types that promote tumor growth, a new study by UT Southwestern researchers suggests. The findings, published in Cell Reports, could lead to new ways to fight breast cancer, a disease diagnosed in more than 300,000 American women each year and which kills nearly 45,000 each year.
“We have identified novel adipocyte-derived cell types in the mammary gland that provide fertile ground for the invasion and growth of breast cancer tumors,” said study leader Philipp Scherer, Ph.D., professor of internal medicine and cell biology and member of the Harold C. Simmons. Comprehensive Cancer Center at UTSW.
Obesity has long been considered a risk factor for breast cancer and a poorer prognosis. Studies have shown that fat cells in close contact with breast tumor cells have an enhanced ability to break down their lipids to provide fuel for invading tumor cells. dr. However, Scherer explained that it is unclear what other roles these adipocytes play in breast cancer progression.
To answer this question, Qingzhang Zhu, Ph.D., an internal medicine instructor and member of the Scherer lab, and his colleagues used a genetic technique that “painted” adipocytes in lab mice so that they glowed a fluorescent color, causing it became possible to monitor these cells in the long term. When the researchers implanted mammary tumors in the mice or genetically engineered the rodents’ own breast cells to turn them into tumor cells, they saw nearby fat cells shrank and take on shapes different from the native adipocytes. Genetic testing to identify which genes were active in these fat cells showed that these cells first went back to an earlier stage of development and then gradually evolved genetic markers of other cell types, including connective tissue cells, muscle cells and immune cells.
Further investigation showed that these altered fat cells encouraged the growth of breast cancer tumors. However, this property also critically depended on their ability to supply energy to neighboring tumor cells. In addition, the properties of the cell types into which fat cells change after losing their lipids and their fat cell identity are important, as they contribute significantly to the local fibrosis, which contributes to the stiffness of breast tissue. When the researchers improved the lipid storage capacity of adult fat cells, they no longer changed into other cell types and no longer promoted tumor growth.
dr. Scherer said 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 look for this signal and look for other ways to manipulate this system to discourage breast cancer growth.
The study is part of a joint initiative by UTSW’s Touchstone Diabetes Center and Harold C. Simmons Comprehensive Cancer Center to better understand the link between cancer risk and obesity.
dr. Scherer holds the Gifford O. Touchstone, Jr. and Randolph G. Touchstone Distinguished Chair in Diabetes Research and the Touchstone/West Distinguished Chair in Diabetes Research.
Other UTSW researchers who contributed to this research include Yi Zhu, Chelsea Hepler, Qianbin Zhang, Jiyoung Park, Christy Gliniak, Gervaise H. Henry, Clair Crewe, Dawei Bu, Zhuzhen Zhang, Shangang Zhao, Thomas Morley, Na Li , Dae-Seok Kim, Douglas Strand, Yingfeng Deng, Ruth Gordillo, Christine M. Kusminski, and Rana K. Gupta.
This study was supported by grants from the National Institutes of Health (R01-DK104789, RC2-DK118620, R01-DK55758, R01-DK099110, R01-DK118620, R01-10 DK127274, and R01-131537).
About UT Southwestern Medical Center
UT Southwestern, one of the nation’s premier academic medical centers, integrates cutting-edge biomedical research with exceptional clinical care and education. The institution’s faculty has received six Nobel Prizes and includes 26 members of the National Academy of Sciences, 17 members of the National Academy of Medicine, and 14 Howard Hughes Medical Institute Investigators. Its full-time faculty of more than 2,900 members is responsible for pioneering medical advances and is committed to quickly translating science-based research into new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 100,000 hospitalized patients, more than 360,000 emergency care cases, and oversee nearly 4 million outpatient visits per year.