Fattening Up Cancer – Morning Sign Out at UCI

Written by Christina Young and Edited Catherine Zhang

Dr. Cecil Fox (Photographer), National Cancer Institute, National Institutes of Health

What is preferable, weight gain by malignant oncogenic tumor or adipose? Known by more general terms, on their own, neither. Although, it begs the question that if one is a disease and the other is fat, which is preferable? Found in connective tissue throughout the body, adipocytes are simply relatively benign fat cells, although they are the basis of obesity when in high concentrations. On the other hand, oncogenic tumors, more commonly known as cancer, are clusters of rapidly replicating cells. Cancer cells come from mutations in the cellular function that inhibit the regulation of the cell cycle, the life cycle of a cell that encodes how much a cell can replicate [1]. In essence, there are more cells created than there are dying, and these cells are not completely stationary either—their potential to move through the bloodstream and relocate the mutation to other areas of the body, or metastasize, can be extremely dangerous to those afflicted. Researchers in the Ishay-Ronen lab in Switzerland are currently working on a type of mammary cancer in mice that is a close cousin of one found in humans in order to push forward the possibility of converting breast cancer cells into fat cells [2].

Metastasized cancer cells can spread everywhere and anywhere in the body, and there are very few constraints as to where they can travel through the bloodstream before being deposited and replicating. Although seemingly unstoppable, the cancer cells cannot act like cancer cells as they travel, and are instead undergoing a process to essentially hide their mutated genes that make them cancerous. The overall process allows the cells to travel freely, despite treatments used to target their stationary sisters. The reciprocal processes known as EMT, or epithelial-mesenchymal transition, and MET, mesenchymal-epithelial transition, act opposite each other in which the stationary cancer cell loses its specific functions and becomes a type of stem cell– a state of a cell in which it has the potential to become nearly any cell in the body. Then, the cells convert back into a cancer cell somewhere down the bloodstream [2]. This mesenchymal transition state has a predisposition to become breast cancer cells, and can be targeted with the signaling protein TGF-β to prevent MET, or the transition back to stationary cancer cells. In doing so, the cells maintain their differentiation potential, and by treatment with insulin and bone morphogenetic protein-2 amongst a number of other proteins, can induce the formation into fat cells, known as adipogenesis [3].

In the scientific community, adipocytes are known for their high regulation of their cell cycle, requiring many different components in order to continue on through the process of replication. This characteristic makes it a near ideal candidate for the prevention of oncogenic expansion [4]. Beyond regulation, adipocytes are also relatively benign and present throughout the body, meaning that moderate buildup in tissue will not greatly inhibit organ function.

In their research, Ishay-Ronen’s lab compared the difference in cancer cell conversion to adipocytes between those in and out of the mesenchymal transition state, looking at the best way to target metastasizing cells. They found that a combination of the drug rosiglitazone and a protein inhibitor for the cellular proliferation of most cancer cells, along with an injected TGF-β protein treatment, exhibited transformation of breast cancer mesenchymal-induced cells into adipocytes most efficiently in pre-clinical settings in mice [2]. Overall, the study looks to revolutionize the approach to breast cancer, which is maliciously present in about 12.4% of women in the U.S., and provide a novel process to eventually reduce the malignancy of all cancers [5]. In doing so, cancer cells and fat cells may eventually be placed on a more comparable basis for choice of treatment in those afflicted.

References:

Share this post:

X (Twitter) Facebook Pinterest LinkedIn Email