Fat cells, or adipocytes, that grow in close proximity to breast cancers can shift into other cell types that promote tumor growth, a latest study by UT Southwestern researchers suggests. The findings, published in Cell Reports, could lead on to latest ways to fight breast cancer, a disease that’s diagnosed in greater than 300,000 U.S. women annually and kills nearly 45,000 annually.

We identified novel adipocyte-derived cell types within the mammary gland that provide a fertile soil for breast cancer tumor invasion and growth.”

Philipp Scherer, Ph.D., 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 occurrence and worse prognosis. Studies have shown that fat cells in close contact with breast tumor cells have an enhanced ability to interrupt down their lipids to offer fuel for invading tumor cells. Nevertheless, Dr. Scherer explained, it has been unclear what other roles these adipocytes play in breast cancer progression.

To reply this query, Qingzhang Zhu, Ph.D., 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 that they glowed a fluorescent color, making it possible to follow these cells long run. When the researchers implanted breast tumors within the mice or genetically manipulated the rodents’ own breast cells to show them into tumor cells, they saw that nearby fat cells shrank and took on forms different from native adipocytes. Genetic testing to discover which genes were lively in these fat cells showed these cells first regressed to an earlier stage in development, then steadily developed genetic markers of other cell types, including connective tissue cells, muscle cells, and immune cells.

Further investigation showed these modified fat cells encouraged breast cancer tumors to grow. Nevertheless, this property also depended critically on their ability to provide energy to neighboring tumor cells. As well as, the properties of the cell types that fat cells morph into after they lose their lipids and their fat cell identity are vital, since they add significantly to the local fibrosis, which contributes to the stiffness of breast tissue. When the researchers enhanced the lipid-storing capability of mature fat cells, they ceased to morph into other cell types and now not promoted tumor growth.

Dr. Scherer said the mechanism for a way adipocytes change into other cell types isn’t yet clear; nevertheless, a chemical signal from tumor cells might be accountable for this phenomenon. He and his colleagues plan to go looking for this signal and search for other ways to govern this technique to discourage breast cancer growth.

Source:

UT Southwestern Medical Center

Journal reference:

Zhu, Q., et al. (2022) Adipocyte mesenchymal transition contributes to mammary tumor progression. Cell Reports. doi.org/10.1016/j.celrep.2022.111362.