How fat can “starve” cancer cells and slow their progress

In order to grow and reproduce quickly, cancer cells need large amounts of energy and molecular building blocks. Many tumors even reprogram their metabolism to capture more glucose, lipids and other nutrients. On the other hand, there are certain adipocytes, the cells responsible for storing energy in the form of fat, that can compete with malignant cells in the task of obtaining the resources that both need to proliferate.

“We implant engineered adipocytes that outcompete tumors in competition for nutrients and show that they can substantially reduce cancer progression,” say the authors of the study, who call this strategy adipose manipulation transplant (AMT).

Researchers have found that adipocytes are not only fat reserves, but are cells with a very active metabolism and can be easily manipulated. Through a procedure, already used in reconstructive surgery, they can be isolated and genetically modified in the laboratory to later be reimplanted into the body.

By forcing the expression of the UCP1 protein, reprogrammed white adipocytes are obtained cells capable of burning large amounts of nutrients such as glucose and fatty acids, at a very accelerated rate.

“Adipocytes engineered to utilize greater amounts of glucose and fatty acids by overexpressing UCP1 were placed next to cancer cells or xenografts, resulting in significant cancer suppression,” the study details.

If these modified cells are cultured alongside tumor cells, cancer growth is markedly reduced. Adipose manipulation transplantation has been tested in mouse models of breast and pancreatic cancer.

Other studies have shown that implanting modified adipocytes significantly slows cancer compared to animals that received unmodified adipocytes.

The method studied has other considerable advantages. On the one hand, the therapy can be activated or deactivated using drugs or cell implants that are easy to use, making it a potential safe and flexible treatment. Furthermore, it is not limited to a single type of tumor metabolism, but can be programmed to consume not only glucose or fatty acids, but also other metabolites, in such a way that the therapy could be adapted to different cancer metabolic profiles.

However, like all preclinical research, the study has its limitations. The results have been obtained in cell cultures and animal models. It is not yet known what number of adipocytes would be necessary to obtain a therapeutic benefit in humans, nor what the complete long-term safety profile would be. It will also be essential to better understand how these fat cells interact with the tumor microenvironment and with the rest of the body.