New research published in the journal Science Signaling suggests surprising insight on melanoma, which although only accounts for 1% of skin cancer diagnoses, is the cause of most skin cancer-related deaths. The study aimed to further understanding on what makes melanoma such an aggressive cancer as it develops and improve therapeutic treatment options.
Led by Professor Carmit Levy and Dr. Tamar Golan, of the Department of Human Genetics and Biochemistry at Tel Aviv University's Sackler School of Medicine, the team analyzed tissue samples from melanoma patients at the Wolfson Medical Center and Tel Aviv Medical Center in Israel.
They looked at how in situ melanoma cells (which refer to the disease when it is still in its early, easily treatable stages) develop as the disease progresses. What they found was surprising: the aggressiveness of cancer (i.e. the metastasis of tumors) correlated with the movement of fat cells from the deeper layers of the skin to the upper dermis layer (and therefore closer to melanoma cells).
The scientists were able to figure out that this switch is trigger by fat cells secrete two cytokines: interleukin-6 and tumor necrosis factor-alpha. Both are proteins capable of altering gene expression.
"Our experiments have shown that the main effect of cytokines is to reduce the expression of a gene called miRNA 211, which inhibits the expression of a melanoma receptor of [transforming growth factor-beta (TGF-beta)], a protein that is always present in the skin," explains Professor Levy. "The tumor absorbs a high concentration of TGF-beta, which stimulates melanoma cells and renders them aggressive."
The American Cancer Society estimates that during 2019, US doctors will diagnose 96,480 new cases of melanoma, and 7,230 people will die from the disease. The disease is much easier to treat when it is in situ; survival rate drops down to 23% as the cancer advances.
"Locked in the skin's outer layer, the epidermis, melanoma is very treatable; it is still stage 1, it has not penetrated the dermis to spread through blood vessels to other parts of the body, and it can simply be removed without further damage," elaborates Professor Levy. "Melanoma turns fatal when it 'wakes up,' sending cancer cells to the dermis layer of skin below the epidermis and metastasizing in vital organs. Blocking the transformation of melanoma is one of the primary targets of cancer research today, and we now know that fat cells are involved in this change. Our findings can serve as a basis for the development of new drugs to halt the spread of melanoma — therapies that already exist, but were never used for this purpose.”