Aggressive breast cancer grows faster in obese environment

April 4, 2017

It’s not just what’s inside breast cancer cells that matters. According to researchers at the University of North Carolina, the environment surrounding cancer cells also drives the disease.

In an abstract that was presented April 3 at the American Association for Cancer Research Annual Meeting, researchers from the UNC Gillings School of Global Public Health reported their preliminary findings that cancer cells grew faster when they were transplanted into fatty, obese tissue. They believe the study can help explain the known link between obesity and cancer by providing evidence that elements of a fatty tissue environment may help cancer to grow.

Dr. Liza Makowski

Dr. Liza Makowski

The research was presented by Liza Makowski, PhD, associate professor in the Gillings School’s Department of Nutrition, and Alyssa J. Cozzo, doctoral student of nutrition. Makowski also is a member of the UNC Lineberger Comprehensive Cancer Center.

“We’re interested in something called the ‘microenvironment,’ which is basically the cells around a tumor and the chemicals those cells produce,” said Makowski. “In breast cancer, we know that the cancer is embedded in very fatty [or adipose] tissue, because the breast is largely made up of adipose tissue. As a person becomes obese, that can change the adipose tissue, also changing the microenvironment so the cancer can start or progress.”

For the study, researchers in the Makowski Lab worked with a type of breast cancer known as triple-negative breast cancer. Researchers transplanted and grew triple-negative breast cancer cells from lean laboratory models into models of three different microenvironments – obese, lean and formerly obese – to observe how tumors grew in these different contexts.

Tumors were significantly larger in the obese models than in the lean models, and also were larger than tumors in formerly obese models that had lost the weight. These findings suggest that weight loss corrected changes to the microenvironment that were helping to drive the cancer.

When the researchers analyzed the gene expression patterns occurring within the tumors themselves, they found that the alterations that had occurred were “extremely subtle,” Makowski said, and could not explain the especially dramatic tumor growth they saw in the obese mice.

“We saw the most changes in the mammary glands around the tumors,” said Cozzo, the study’s first author. “This implies that the microenvironment surrounding the tumor can be a driver of tumor growth, even when the tumor cells and the other cells that make up the tumor itself are relatively similar.”

These findings have important implications for understanding the link between obesity and cancer.

“Our take-home message for this study was that, indeed, the obese microenvironment (the mammary gland surrounding the tumor) can drive tumor growth even when the tumor cells come from a lean mouse,” Makowski said. “Critically, the obese environment can be partially or completely reversed by weight loss. It’s as if the cells do not ‘remember’ the obese exposure.”

In addition to Cozzo and Makowski, other authors from the Gillings School’s Department of Nutrition include Ottavia Zattra, undergraduate student, and Alex J. Freemerman, PhD, research associate.

This study was supported by the National Institutes of Health, the University Cancer Research Fund, a Chancellor’s Fellowship and the Royster Society of Fellows.


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Gillings School of Global Public Health contact: David Pesci, director of communications, (919) 962-2600 or dpesci@unc.edu

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