Transforming Melanoma Into a Nonthreatening Illness

A new study is suggesting that it may be possible to turn melanoma into a nonthreatening, easily curable disease. 

Researchers at Tel Aviv University (TAU) have published a paper in the journal Nature Cell Biology suggesting that before spreading to other organs, a melanoma tumor sends out tiny vesicles containing molecules of microRNA. These molecules induce morphological changes in the dermis in preparation for receiving and transporting the cancer cell. The researchers also found chemical substances that can stop the process and potentially promising drug candidates. 

"The threat of melanoma is not in the initial tumor that appears on the skin, but rather in its metastasis, in the tumor cells sent off to colonize in vital organs like the brain, lungs, liver and bones," said research leader Carmit Levy, PhD, of the Department of Human Molecular Genetics and Biochemistry at TAU's Sackler School of Medicine, Tel Aviv, Israel, in a news release. "We have discovered how the cancer spreads to distant organs and found ways to stop the process before the metastatic stage."

Levy and her colleagues examined pathology samples taken from melanoma patients. They found melanoma originates in the epidermis and becomes metastatic after invasion into the dermis. In melanoma in situ, the researchers found the melanosomes carry microRNAs into primary fibroblasts triggering significant changes. These changes include increased proliferation, migration, and proinflammatory gene expression.   

In addition, the researchers report that melanosomal microRNA-211 directly targets IGF2R and leads to MAPK signaling activation. This cascade of events encourages melanoma growth. However, the researchers demonstrated that melanosome release inhibitors may put the brakes on the whole process.

The researchers looked for substances that could intervene and block the process in its earliest stages. They found two such chemicals that were successfully tested in the lab. The first one (SB202190) inhibits the delivery of the vesicles from the melanoma tumor to the dermis. The second (U0126) prevents the morphological changes in the dermis even after the arrival of the vesicles.

The finding may open the door to a way of diagnosing or possibly staging melanoma patients in the future. The researchers report that the observed changes in the dermis, as well as the vesicles themselves, may be used as powerful indicators for early diagnosis of melanoma. Levy said these preliminary findings are an important step on the road to a full remedy, rendering melanoma into a nonthreatening, easily curable disease.

Melanoma is the most aggressive and lethal type of skin cancer. The number of diagnosed cases has been on the rise for the past 3 decades and there has been a growing concern worldwide.