Researchers at Tel Aviv University, led by Prof. Carmit Levy and Dr. Tamar Golan of the Department of Human Genetics and Biochemistry at TAU’s Sackler School of Medicine, have discovered that fat cells are involved in the transformation that melanoma cells undergo from cancer cells of limited growth in the epidermis to lethal metastatic cells attacking patients’ vital organs.
“They have answered a major question that has preoccupied scientists for years,” explains Prof. Levy. “What makes melanoma change form, turning aggressive and violent? Locked in the skin’s outer layer, the epidermis, melanoma is very treatable; it is still Stage 1, it has not penetrate the dermis to spread through blood vessels to other parts of the body; also it can simply be remove without further damage.
Samples from melanoma patients
“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 fat cells are involve in this change.” The research was conduct in collaboration with several senior pathologists: Dr. Hanan Vaknin of Wolfson Medical Center, and Dr. Dov Hershkowitz and Dr. Valentina Zemer of Tel Aviv Medical Center.
The study was on publish July 23 in Science Signaling and is feature on the journal’s cover. In the study, the researchers examine dozens of biopsy samples taken from melanoma patients at Wolfson Medical Center and Tel Aviv Medical Center, and observe a suspicious phenomenon: fat cells near the tumor sites. “They asked ourselves what fat cells were doing there and began to investigate,” adds Prof. Levy. “They place the fat cells on a petri dish near melanoma cells and followed the interactions between them.”
The researchers observe fat cells transferring proteins called cytokines; so to affect gene expression, to the melanoma cells. “Our experiments have shown that the main effect of cytokines; which is to reduce the expression of a gene called miRNA211; which inhibits the expression of a melanoma receptor of TGF beta, a protein that is always present in the skin,” says Prof. Levy. “The tumor absorbs a high concentration of TGF beta, which stimulates melanoma cells and renders them aggressive.”
Blocked metastases formation
Critically, the researchers have also find a way to block this transformation. “It is important to note that they find the process reversible in the laboratory: When we remove the fat cells from the melanoma; so the cancer cells calm down and stop migrating,” adds Prof. Levy. A trial of mouse models of melanoma yield similar results: When miRNA211 was repressed, metastases were find in other organs; so while re-expressing the gene block metastases formation.
In the search for a potential drug base on the new discovery; so the researchers experiment with therapies that are known to inhibit cytokines and TGF beta; but which have never before use to treat melanoma. “They are talking about substances that are currently being study as possible treatments for pancreatic cancer, and are also in clinical trials for prostate, breast, ovarian and bladder cancers,” Dr. Golan said.
“They saw that they restrain the metastatic process, and that the melanoma return to its relatively ‘calm’ and dormant state.””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 use for this purpose,” concludes Prof. Levy. “In the future, we are seeking to collaborate with drug companies to enhance the development of the metastatic melanoma prevention approach.”