Why does melanoma, which accounts for 2 percent of skin cancer cases, cause almost all skin cancer deaths? Why have melanoma rates in the US been rising rapidly over the last 30 years? What is melanoma's modus operandi?
A new study at Tel Aviv University (TAU), published in Molecular Cell and reported in Drug Discovery & Development, offers insight into the exact trigger that causes melanoma cancer cells to transform from non-invasive cells to invasive killer agents, showing the exact place in the process where "traveling" cancer turns deadly. Dr. Carmit Levy of the Department of Human Genetics and Biochemistry at TAU's Sackler School of Medicine led the study, which was conducted by a team of researchers from TAU, the Technion Institute of Technology, the Sheba Medical Center, the Institut Gustave Roussy and The Hebrew University of Jerusalem
According to skincancer.org, melanoma is the most dangerous form of skin cancer. Cancerous growths develop when unrepaired DNA damage to skin cells triggers mutations (genetic defects) that cause the skin cells to multiply quickly and form malignant tumors that originate in the pigment-producing melanocytes in the basal layer of the epidermis. Melanomas, which look like moles, sometimes develop from moles. Most are black or brown, but they can also be flesh-colored, pink, red, purple, blue or white. Melanoma, which is caused mostly by intense, occasional UV exposure, especially in those who are genetically predisposed to the disease, kills an estimated 9,940 people in the US annually
Melanoma that is caught in time can be removed and the patient's life saved, but if it invades the bloodstream, turning metastatic, the treatment is aggressive and not always successful. Dr. Levy wanted to know when and how the transformation into aggressive invasion took place. As he explained, "To understand melanoma, I had to obtain a deep understanding about the structure and function of normal skin. Melanoma is a cancer that originates in the epidermis, and in its aggressive form it will invade the dermis, a lower layer, where it eventually invades the bloodstream or lymph vessels, causing metastasis in other organs of the body. But before invading the dermis, melanoma cells surprisingly extend upward, then switch directions to invade. It occurred to me that there had to be a trigger in the microenvironment of the skin that made the melanoma cells 'invasive.' Using the evolutionary logic of the tumor, why spend the energy going up when you can just use your energy to go down and become malignant?"
The researchers collected samples of normal skin cells and melanoma cells from patients at hospitals around Israel, mixed normal and cancerous cells and performed gene analysis expression to study the traveling cancer's behavior. They discovered that, completely independently of any mutation acquisition, the microenvironment alone was the trigger for melanoma metastasis.
According to Dr. Levy "Normal skin cells are not supposed to 'travel.' We found that when melanoma is situated at the top layer, a trigger sends it down to the dermis and then further down to invade blood vessels. If we could stop it at the top layer, block it from invading the bloodstream, we could stop the progression of the cancer."
The researchers discovered that the direct contact of melanoma cells with the remote epidermal layer triggered an invasion by activating "Notch signaling," which activates a set of genes that stimulates changes in melanoma cells, making them invasive. They found that when a molecule expressed on a cell membrane - a spike on the surface of a cell, called a ligand - comes into contact with a melanoma cell, it transforms the cell into an invasive, deadly agent.
Dr. Levy concluded, "Melanoma is a cancer with a very long gestation period. If you can provide a simple kit with precise answers, you can catch it at the beginning stage and hopefully save lives."