The Jerusalem Post

TAU: Fat cells can trigger melanoma

- • By SONIA EPSTEIN

A 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 the Department of Human Genetics and Biochemist­ry at the Sackler Medical School of Tel Aviv University.

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. Cytokines 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 fairskinne­d, 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 adds 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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