After implantation, they outpaced cancer cells in the competition for resources, defeating five different types of malignant cells in laboratory experiments.
Liposuction and plastic surgery are rarely mentioned alongside cancer.
Yet, these very procedures inspired a new approach to cancer treatment that utilizes engineered fat cells capable of depriving tumors of nutrients.
Researchers from the University of California, San Francisco, employed CRISPR gene-editing technology to transform ordinary white fat cells into "brown" cells that eagerly consume calories to produce heat. These cells were then implanted near tumors, similar to how plastic surgeons inject fat from one body part to augment another. The fat cells absorbed all the nutrients, leading to the starvation of most tumor cells. This method was effective even when the fat cells were implanted in mice far from their tumor sites.
“We routinely remove fat cells through liposuction and reintroduce them via plastic surgery,” says Nadav Ahituv, Ph.D., director of the UCSF Institute for Human Genetics and professor in the Department of Bioengineering and Therapeutic Sciences. He is the lead author of a study published in February in Nature Biotechnology. “These fat cells can be easily and safely managed in the lab and reinserted into the body, making them an attractive platform for cell therapy, including for cancer.”
Ahituv and his colleagues were already aware of research showing that cold exposure could suppress cancer in mice. The scientists concluded that cancer cells starve because cold activates brown fat cells, which utilize nutrients to generate heat.
However, cold treatment is not suitable for cancer patients with compromised health.
Thus, Ahituv and his team turned to the idea of using brown fat, believing they could engineer it to burn enough calories even in the absence of cold, depriving tumors of the fuel they need to grow.
The researchers explored genes that lie dormant in white fat cells but are active in brown fat cells, hoping to identify those that would convert white fat cells into the most ravenous brown fat cells.
A gene called UCP1 topped the list.
Next, the researchers grew brown fat cells with the UCP1 gene alongside cancer cells in a Petri dish. The cancer cells were at the bottom, while the fat cells were above them, in separate compartments that kept the cells apart but allowed them to exchange nutrients.
The results were astonishing.
Nadav Ahituv, lead researcher
Brown fat cells countered two different types of breast cancer cells, as well as cells from colon, pancreatic, and prostate cancers.
However, the researchers still did not know whether the implanted brown fat cells would function effectively in real-world conditions.
To test how they would perform in human tissues, the scientists collected samples from breast mastectomies containing both fat and cancer cells.
Since the breast contains a lot of fat, the researchers decided to take fat from the same patient, modify it, and grow it in a well alongside her own breast cancer cells.
These brown fat cells from the same patient effectively dealt with breast cancer cells in Petri dishes and when co-implanted into mouse models.
Knowing that cancer tumors have specific nutrient preferences, the researchers engineered the fat to consume particular nutrients. For example, some forms of pancreatic cancer "favor" uridine. Thus, they programmed the fat to consume only uridine, and it easily outperformed pancreatic cancer cells.
This indicates that fat can be tailored to the dietary preferences of any type of cancer.
Fat cells have numerous advantages when it comes to cell therapy.
They are easily obtained from patients. They grow well in the lab, and they can be engineered to express various genes and perform different biological functions. They behave well after being reintroduced into the body, remaining at the implantation site and interacting with the immune system.
This fact is supported by decades of progress in plastic surgery.
Fat cells can also be programmed to send signals or perform more complex tasks. Their ability to combat cancer, even when not located near the tumor, could prove invaluable for treating hard-to-reach cancers like glioblastoma, which affects the brain, as well as many other diseases.