Altered fat cells may fuel breast cancer tumor growth

Researchers investigated what happens to fat cells near breast cancer tumors. They found that, when near tumor cells, fat cells lose their lipid content, transition into other cell types, and fuel tumor growth.

Further research is needed to understand how fat cells transition into other cell types.

These findings suggest that approaches to stop fat cells from changing could suppress tumor progression.

The American Cancer Society estimates that around 287,850 women will receive a breast cancer diagnosis in 2022. One in 8 women are also estimated to develop breast cancer in their lifetime.

Some studies suggest that obesity is a risk factor for breast cancer occurrence and a worse prognosis. However, other studies report minimal effects from obesity on breast cancer recurrence and survival.

These mixed results raise questions on the underlying mechanisms potentially linking breast cancer and obesity.

In breast cancer, tumor cells are nearby fat cells, known as mammary adipocytes. Adipocytes have a high degree of plasticity and can change depending on their environment.

For example, studies have found that adipocytes near tumor cells lose their lipid content and that ‘lipid storing’ white fat cells are replaced with beige ‘lipid-burning’ adipocytes.

How exactly fat and tumor cells interact remains unknown. Further research into this could lead to new treatment options for breast cancer.

Recently, researchers used a genetic technique to monitor how adipocytes and breast tumors interact in mice.

“The study shows that fat cells are not simple bystander cells but play a dynamic role in the development of breast cancer,” Dr. Jane Visvader, professor of cancer biology and stem cells at the Walter and Eliza Hall Institute of Medical Research (WEHI) at the University of Melbourne, who was not involved in the study, told Medical News Today.

“Interestingly, fat cells were shown to assume the properties of other mesenchymal lineages to fuel tumor growth in models of breast cancer. These findings have implications for understanding the complex linkage between obesity and breast cancer risk,” she added.

The study was published in Cell Reports.

For the study, the researchers used a genetic technique to permanently ‘stained’ mature adipocytes in mice. In doing so, they were able to track their development over time, as well as that of cells derived from them.

The researchers then either implanted breast tumors into mice or genetically manipulated their own breast cells to become tumor cells.

They saw that fat cells lost their lipid content when next to either implanted or genetically induced breast cancer cells.

From genetic tests, the researchers then found that fat cells first regressed to an earlier developmental stage before gradually developing genetic markers for other cell types, including connective tissue cells, muscle cells, and immune cells.

These depleted and genetically-altered fat cells then fueled breast cancer growth.

The researchers also found that the fat-depleted fat cells contribute to local fibrosis—thickening or scarring of tissue—which contributes to breast tissue stiffness.

They noted, however, that it may be possible to reverse this process. After enhancing the lipid-string capacity of mature fat cells, the researchers noted that they stopped morphing into other cell types and no longer supported tumor growth.

How fat cells morph into inflammatory cells

The researchers wrote that previous studies have found that inflammation is often elevated in the tumor microenvironment and is a key contributor to the tumor environment.

They also noted that the tumor microenvironment likely morphs altered cells toward inflammatory cells, as well as proteins and other molecules that surround and support cells and tissues.?

When asked how adipocytes might change into other cell types, Dr. Philpp E. Sherer, professor of internal medicine at the University of Texas, one of the study’s authors, told MNT:

“Nearby tumor cells force adipocytes to give up their lipid fuel to allow growth. They induce lipolysis in the adipocytes, which prompts them to release free fatty acids as fuel.”

“But there is more. We do not know the specific factor that tumor cells release to induce lipolysis and de-differentiation,” he noted.

“Once [transitioned into] adipocyte precursors, these cells are subject to additional signals in the tumor stroma- supporting tissues surrounding the tumor that direct them to become myofibroblasts—a cell type essential for healing—and additional cell types. So the tumor cell creates its own microenvironment by supporting itself by cell types that support the growth of the tumor lesion,” he added;?

The researchers concluded that approaches that prevent adipocytes from transitioning into other cell types might suppress tumor growth and spread.

Dr. Scherer noted that a key limitation of the study is that they have not yet identified specific tumor-derived factors that trigger adipocytes to transition.

“Furthermore, we present mostly preclinical data in mouse models along with the analysis of some clinical samples where we see correlations that are consistent with our proposed model. The clinical relevance of these findings will have to await the identification of the factors that drive this process,” he added.