Tumors are nutrient hogs. The faster proliferation of cancer cells versus normal cells comes from their more aggressive consumption of nutrients like glucose and fatty acids. Hence, to prevent their growth and starve them to death, either their access to nutrients should be cut off or normal cells should be able to outcompete them for nutrients. The latter is the general idea behind the proposed cancer treatment called Adipose Manipulation Transplantation.
Adipose Manipulation Transplantation and Metabolism-Based Approach to Treating Cancer: Transplanting Engineered Fat Cells as Possible Novel Cancer Therapy
Background
Researchers headed by Nadav Ahituv from the University of California, San Francisco wondered what would happen if normal cells are given the ability to outcompete cancer cells for nutrients. This curiously drew their attention to adipocytes or fat cells. These cells, especially the white fat cells, are abundant and easy to collect. These cells are also easy to engineer.
Previous studies found that cold temperatures could suppress tumor growth in mice. This is due to the fact that exposure to cold activates brown fat cells. These fat cells consume large amount of glucose and produce heat. Other studies have proposed either activating or transplanting brown fat cells as part of a novel weight loss procedure.
Nevertheless, to bank aforementioned information, the researchers engineered white fat cells to trigger certain genes and turn them into beige fat cells using CRISPR. These genes mimic what brown fat does when exposed to cold. Activating a specific gene called Uncoupling Protein 1 or UCP1 gene made fat cells much hungrier for glucose and fatty acids.
The engineered fat cells were placed next to tumors in different lab models. The whole process is called Adipose Manipulation Transplantation. Remember that the goal was to position normal cells that can absorb more nutrients than usual next to cancer cells and observe how this competition for nutrients will affect cancer growth and proliferation.
Findings
The researchers specifically chose to work with white fat because it is abundant in the body and more accessible than brown fat. Note that brown adipose tissues become less active with age. It is also worth mentioning that engineering white fat cells to behave like brown fat cells is easier and more practical than brown fat activation via cold therapy.
Initial experiments in lab dishes showed dramatic cancer cell death when exposed to the engineered fat cells. The effectiveness of the therapy was confirmed in living organisms using a mouse model. The engineered fat cells could even exert their effect and starve cancer cells even when implanted far from the tumor. The following are the key results:
• Impact on Tumor Growth: Tumor growth was significantly reduced in both lab dishes or in vitro and mouse models or in vivo with either breast cancer or pancreatic cancer. The tumors also had less blood vessel growth or angiogenesis and lower oxygen deprivation or hypoxia. These two are needed for cancer to thrive.
• Human Breast Cancer Samples: Another laboratory model involving human breast cancer samples showed that co-culturing tumor cells with these engineered fat cells reduced cancer progression and cell division.
• Flexible Delivery and Control: The engineered fat cells could be induced to outcompete tumors using a chemical switch like tetracycline. These cells can also be delivered within a cell-scaffold platform to implant them near the tumor.
• Specific Customizations: Targeting specific nutrients to target the unique metabolic needs of different cancers is also possible. Engineered fat cells were tweaked to be hungry for uridine. Some pancreatic cancers depend on this nutrient. The customized fat cells were able to inhibited the growth of uridine-dependent pancreatic cancer.
Implications
The prime characteristic of Adipose Manipulation Transplantation is that it is a metabolism-based approach to treating cancer. It involves targeting the unique metabolic needs of cancer cells to slow or stop their growth. Hence, instead of killing cancer cells with drugs, radiation, or surgery, this method staves tumors by disrupting how cancer cells obtain and use energy.
A metabolism-based therapy like Adipose Manipulation Transplantation has several advantages and unique benefits. These include being less toxic than chemotherapy and radiotherapy, ability to target the fundamental need for cancer to consume large amounts of nutrients, possibility to work with different types of cancer, and several customization potentials.
FURTHER READINGS AND REFERENCES
- Chen, Z., and Kang, Y. 2023. “Cold Snap for Cancer: Cold-Induced Brown Fat Thermogenesis Starves Tumor Growth.” Signal Transduction and Targeted Therapy. 8(1). DOI: 1038/s41392-022-01284-5
- Nguyen, H. P., An, K., Ito, Y., Kharbikar, B. N., Sheng, R., Paredes, B., Murray, E., Pham, K., Bruck, M., Zhou, X., Biellak, C., Ushiki, A., Nobuhara, M., Fong, S. L., Bernards, D. A., Lynce, F., Dillon, D. A., Magbanua, M. J. M., Huppert, L. A., … Ahituv, N. 2025. “Implantation of Engineered Adipocytes Suppresses Tumor Progression in Cancer Models.” Nature Biotechnology. DOI: 1038/s41587-024-02551-2