Fat cells allow melanoma cells to penetrate the dermis, from which they spread, causing fatal metastases in vital organs, TAU researchers say
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.
“We 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 penetrated the dermis to spread through blood vessels to other parts of the body and it can simply be removed without further damage.
“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 involved in this change.””
The research was conducted 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 published July 23 in Science Signaling and is featured on the journal’s cover.
In the study, the researchers examined dozens of biopsy samples taken from melanoma patients at Wolfson Medical Center and Tel Aviv Medical Center, and observed a suspicious phenomenon: fat cells near the tumor sites.
“We asked ourselves what fat cells were doing there and began to investigate,” adds Prof. Levy. “We placed the fat cells on a petri dish near melanoma cells and followed the interactions between them.”
The researchers observed fat cells transferring proteins called cytokines, which affect gene expression, to the melanoma cells.
“Our experiments have shown that the main effect of cytokines 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.”
Critically, the researchers have also found a way to block this transformation.
“It is important to note that we found the process reversible in the laboratory: When we removed the fat cells from the melanoma, the cancer cells calmed down and stopped migrating,” adds Prof. Levy.
A trial of mouse models of melanoma yielded similar results: When miRNA211 was repressed, metastases were found in other organs, while re-expressing the gene blocked metastases formation.
In the search for a potential drug based on the new discovery, the researchers experimented with therapies that are known to inhibit cytokines and TGF beta, but which have never before been used to treat melanoma.
“We are talking about substances that are currently being studied as possible treatments for pancreatic cancer, and are also in clinical trials for prostate, breast, ovarian and bladder cancers,” Dr. Golan said. “We saw that they restrained the metastatic process, and that the melanoma returned 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 used 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.”
The Latest on: Melanoma
via Google News
The Latest on: Melanoma
- Miles for melanoma: taking steps towards a cureon October 28, 2019 at 3:33 pm
I asked Sue Brown at her home. "It is a grief that never fully goes away," said the Olivenhain resident. Sue watched my story in March when melanoma was cut out of my back, and she couldn't help but ...
- Bennett, Jane Marie Fordon October 28, 2019 at 2:00 pm
SHAWANO - Jane Marie Ford Bennett, age 66, passed away at home on Thursday, Oct. 10, 2019 with her loving husband by her side following a courageous battle with metastatic melanoma. Jane was born on ...
- Rho-mediated signaling promotes BRAF inhibitor resistance in de-differentiated melanoma cellson October 28, 2019 at 1:46 pm
Over half of cutaneous melanoma tumors have BRAF V600E/K mutations. Acquired resistance to BRAF inhibitors (BRAFi) remains a major hurdle in attaining durable therapeutic responses. In this study we ...
- 'None of us were ready': Graphic photos show the reality of skin canceron October 28, 2019 at 11:45 am
Perth beautician Fallon Glossop took to Facebook urging others to practice sun safety after a small mole on her husband Ryan Glossop’s back turned out to be melanoma. “This subject is quite raw for me ...
- Urethral Involvement Key in Vulvar Melanoma Recurrenceon October 25, 2019 at 4:16 am
Urethral involvement has been singled out for the first time as a key factor in the risk for recurrence in women with vulvar malignant melanoma, an observational study indicates. That and tumor depth ...
- Uveal melanoma-associated survival in Scotlandon October 24, 2019 at 4:06 pm
Describe recorded cause of death and long-term melanoma-specific survival of patients with UM, according to an analysis of SOOS data 2. Determine long-term cancer-specific and all-cause survival of ...
- Metastatic Melanoma: What a Change in Prognosison October 24, 2019 at 10:33 am
"A few of us were sitting together in a room, and I said that I wanted to focus on melanoma," Friedlander said. "One of my friends said something to the effect of 'Oh, so you're going to focus on ...
- New dosing schedules for Bristol-Myers Opdivo for melanoma OK'd in Europeon October 24, 2019 at 4:41 am
The European Commission has approved a flat dosing of schedule of 240 mg infused over 30 minutes every two weeks or 480 mg infused over 60 minutes every four weeks for Bristol-Myers Squibb's (NYSE:BMY ...
- Dad's 'sun spot' is a melanoma: doctors remove MASSIVE chunk of skinon October 20, 2019 at 3:26 am
A father who had an enormous chunk of his neck gouged out to remove a deadly melanoma has issued a warning to all sun seekers. Ryan Glossop, 37, made the potentially life-saving decision to get his ...
- Early detection of ocular melanoma saves Elkhart man's visionon October 17, 2019 at 3:50 pm
"After she had done it, she said, 'I found something,' and she drew a picture of the inside of my eyeball and showed me little spaces. 'This is back here, and I believe it's a kind of melanoma,'" Jim ...
via Bing News