Underlying mechanisms of skin cancer reveal potential avenue to cure melanoma.
In a groundbreaking discovery, researchers unveiled the underlying metastatic mechanisms of melanoma, findings that could lead to a cure.
Before melanoma starts to spread to other parts of the body, the tumor will send out tiny vesicles that contain molecules of microRNA. These vesicles induce morphological changes in the dermis in preparation for receiving and transporting the cancer cells, according to a study published in Nature Cell Biology.
“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 lead researcher Carmit Levy. “We have discovered how the cancer spreads to distant organs and found ways to stop the process before the metastatic stage.”
According to the Skin Cancer Foundation, 1 person dies from melanoma every 52 minutes, and the number of cases has been steadily increasing over the past 3 decades.
In the current study, researchers set out to find the mechanisms behind the spread of this deadly cancer. They started by examining pathology samples from melanoma patients.
“We looked at samples of early melanoma, before the invasive stage,” Levy said. “To our surprise we found changes in the morphology of the dermis — the inner layer of the skin – that had never before been reported. Our next task was to find out what these changes were, and how they related to melanoma.”
It’s important to note that for years, researchers have been aware that melanoma forms in the epidermis. During the early stages of the cancer, it is unable to disperse colonizing cancer cells, because it does not have any access to blood vessels.
Since there are no blood vessels in the epidermis, the tumor needs to connect with blood vessels that run through the dermis, but how this happens was unknown.
“We found that even before the cancer itself invades the dermis, it sends out tiny vesicles containing molecules of microRNA,” Levy said. “These induce the morphological changes in the dermis in preparation for receiving and transporting the cancer cells. It then became clear to us that by blocking the vesicles, we might be able to stop the disease altogether.”
Once researchers were able to identify these mechanisms, they continued to look for substances that could intervene and block the process in its earliest stages. Two chemicals were found to fit the bill: SB202190 and U0126.
SB202190 inhibits the melanoma tumor from delivering the vesicles to the dermis, while U0126 prevents the morphological changes in the dermis, even after the vesicles arrive. Both of these substances tested successfully in the lab, and may serve as promising candidates for future drugs, according to the study.
Furthermore, the changes in the dermis and the vesicles themselves, can serve as powerful indicators for early diagnosis of melanoma.
“Our study is an important step on the road to a full remedy for the deadliest skin cancer,” Levy said. “We hope that our findings will help turn melanoma into a nonthreatening, easily curable disease.”