Shape-shifting fat cells provide fertile ground for breast tumor invasion and growth

A new study by researchers at Southwestern University has found that fat cells, or fat cells that grow near breast cancers, can transform into other cell types that promote tumor growth. The findings, published in Cell Reports, could lead to new ways to combat breast cancer, a disease that is diagnosed in more than 300,000 American women each year and kills nearly 45,000 annually.

We identified new types of adipocyte-derived cells in the mammary gland that provide fertile soil for breast cancer tumor invasion and growth.”

Philip Shearer, PhD, study leader, 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 worse prognosis. Studies have shown that fat cells in close contact with breast tumor cells have an enhanced ability to break down their own fat to provide fuel for the invasion of cancer cells. However, Dr. Shearer explained that it was not clear what other roles these adipocytes play in the development of breast cancer.

To answer this question, Qingzhang Zhu, Ph.D., an internal medicine instructor and member of Scherer’s lab, and colleagues used a genetic technique that “painted” adipocytes in lab mice so that they glow in a fluorescent color, making it possible to follow these cells long-term. When researchers transplanted breast tumors into mice or genetically manipulated rodent breast cells to turn them into tumor cells, they noticed that nearby fat cells shrank and took on different shapes than the original fat cells. Genetic testing to identify the active genes in these fat cells showed that these cells first regressed to an early stage of development, and then gradually developed genetic markers for other cell types, including connective tissue cells, muscle cells, and immune cells.

Further investigation showed that these altered fat cells encouraged breast cancer tumors to grow. However, this property has also critically depended on its ability to provide energy to neighboring tumor cells. In addition, the characteristics of the types of cells that fat cells turn into after they lose their fat and the identity of fat cells are important, as they add significantly to localized fibrosis, which contributes to the hardening of breast tissue. When the researchers boosted the ability of mature fat cells to store fat, they stopped converting into other cell types and no longer promoted tumor growth.

Dr. Shearer said the mechanism of changing adipocytes into other cell types is not yet clear. However, a chemical signal from the tumor cells is probably responsible for this phenomenon. He and his colleagues plan to search for this signal and find other ways to manipulate this system to inhibit breast cancer growth.


Journal reference:

Chu, S.; et al. (2022) Adipocyte mesenchyme transition contributes to breast tumor development. Cell reports.