As If I Needed Another Reason to Hate My Fat Cells

Those of us not blessed with a high-octane metabolism already know the battle with fat cells is a miserable trench-warfare slog through the produce aisle. But new research from Tel Aviv University gives us even more reason to be suspicious of those fat cells. Apparently, they are implicated in the transition that surface-level melanoma cells undergo when they metastasize.

The headline in the article says it bluntly, “Fat triggers metastasis”. When melanoma is only located in the upper layers of the skin, it is usually just a matter of excising it and the patient gets to go on their merry way. But when those cells migrate into the bloodstream and set up shop in organs like the brain, liver, or lungs, that’s when things get very messy. Scientists had puzzled over how those melanoma cells transformed – migrating from the epidermis to those distant organs. Something had to play a part in making something only skin deep penetrate into the body, right?

Professor Carmit Levy and Dr. Tamar Golan of the Department of Human Genetics and Biochemistry at TAU’s Sackler School of Medicine led a team of researchers to try to figure out what in the human body could be that double agent. They looked at biopsies performed on melanoma tumors and discovered that where there’s melanoma, there are fat cells. That piqued their curiosity so they performed an interesting experiment: they played the equivalent of a yenta, putting melanoma cells and fat cells in close proximity to each other and watched their interaction.

Turns out that fat cells are pretty damn generous, transferring proteins called cytokines to melanoma cells. What are cytokines? Basically it’s the broad term for proteins involved in immune cell signaling, regulating your body’s immune response. In this case, the cytokines the fat cells gifted to melanoma cells reduce the expression of the miRNA211 gene. So what, you’re thinking… Well, that gene blocks TGF beta, another protein that’s on your skin. OK, but so what, you’re still thinking… TGF beta can then be absorbed by melanoma cells in much higher than usual doses and let’s just say that adding TGF beta to melanoma cells is like adding a keg of beer to a “just about out of control already” frat party. As Professor Levy states, “The tumor absorbs a high concentration of TGF beta, which stimulates melanoma cells and renders them aggressive.”

Just like out-of-control frat parties, climate change, and the zombie apocalypse, aggressive melanoma is not something we want in our lives. What we do want is a way to block that TGF beta, am I right? Well guess what? If you just remove the fat cells, you remove that whole “melanoma turning into the Incredible Hulk” transformation process. Problem solved! Just liposuction every inch of fat out of your body and you’re good!

Wait, we actually need fat in our bodies to do pesky stuff like keep us warm, protect our organs (when they’re not giving melanoma a backstage pass to aforementioned organs), and you know, keep us alive. So after verifying the results actually happened IRL by using mice experiments, the scientists knew that if there were some medications that reinstated that TGF beta block, they may be on to something interesting.

Lo and behold, there are potential treatments for pancreatic, prostate, breast, ovarian, and bladder cancers currently being studied that inhibit cytokines and TGF beta; they just never were investigated to potentially treat melanoma… until now, that is.