Fat cells can trigger melanoma, says TAU study

When fat cells were removed from the melanoma in laboratory tests, the cancer cells "calmed down and stopped migrating."

By SONIA EPSTEIN
July 24, 2019 20:10
2 minute read.
Tel Aviv University Sackler School of Medicine

Tel Aviv University Sackler School of Medicine. (photo credit: PIKI WIKI)

A new study from Tel Aviv University reports that fat cells play a key role in the process that transforms the darkened skin spots called melanomas into lethally cancerous cells, offering new insights into how to prevent the disease.

Fat cells release proteins called cytokines, which can work against the mechanisms that repress tumors in normally functioning cells.

The research, published July 23 in Science Signaling, was led by Prof. Carmit Levy and Dr. Tamar Golan of TAU's Department of Human Genetics and Biochemistry at the Sackler Medical School.

Levy and Golan collaborated with senior pathologists Dr. Hanan Vaknin of Wolfson Medical Center and Dr. Dov Hershkowitz and Dr. Valentina Zemer of Tel Aviv Medical Center, to obtain biopsy samples from dozens of melanoma patients at the two medical centers.
When they noticed fat cells near the tumor sites, they decided to investigate further the interaction between the two cell types.
Cytokines, the proteins released by fat cells, work against a cell’s cancer-repression mechanisms. They down-regulate the expression of a gene called miRNA211, which in turn reduces the expression of a melanoma receptor for TGF beta, a protein involved in cell proliferation.

With a high concentration of TGF beta, melanoma cells can become metastatic, spreading to vital internal organs like the liver, lungs and brain.

Crucially, the process proved reversible: when fat cells were removed from the melanoma in laboratory tests, the cancer cells “calmed down and stopped migrating,” Levy said.

A similar phenomenon was observed in a trial with mouse models of melanoma. When miRNA211 was repressed, metastatic melanoma was found in other organs – but when it was re-expressed, the gene blocked metastases formation.

These findings do not directly indicate that those with more body fat are at a greater risk of contracting melanoma, which is most commonly found in fair-skinned, red-haired people of all body types.

“I don’t know whether the effect of fat cells on melanoma depends on the amount of fat cells,” Levy said. “It’s a very good question, but we haven’t looked at it.”

She added that there is a strong correlation between obesity and a risk of cancer generally, but there is no conclusive explanation as to why.

“Maybe our research is helping understand that,” she said.

For now, the team is more focused on using existing drugs that inhibit cytokines and TGF beta to try to prevent melanomas from developing into cancer.

While these drugs have been studied as possible treatments for pancreatic cancer – and are also in clinical trials for prostate, breast, ovarian and bladder cancers – they have not been used to prevent the development of metastatic melanoma.

The drugs Galunisertib and Avid200 both proved effective in reducing the progression of melanoma, and the researchers are now hoping to develop these into a drug that people at risk of melanoma can apply to their skin to block cancer development.

“We’re talking about prevention, rather than treatment,” Levy says. She suggests that these drugs, which are currently being studied as treatments for later stages of cancer, might also be important in preventing those cancers, based on the findings of her research.
“It’s about thinking differently,” she said. “It opens new research into other kinds of cancer. There are many potential directions for this.”


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