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Melanoma MicroRNA Trafficking May Control Tumor Primary Niche Formation

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Key Points

  • Researchers found that even before the cancer itself invades the dermis, it sends out tiny vesicles containing molecules of microRNA. These actions induce morphologic changes in the dermis in preparation for receiving and transporting the cancer cells.
  • The team found two chemicals that may block this process: One (SB202190) inhibits the delivery of the vesicles from the melanoma tumor to the dermis, and the second (U0126) prevents the morphologic changes in the dermis even after the arrival of the vesicles.
  • The changes in the dermis, as well as in the vesicles themselves, can also be used as powerful indicators for early diagnosis of melanoma.

Researchers at Tel Aviv University (TAU) may have unraveled the metastatic mechanism of melanoma. According to a paper published by Dror et al in Nature Cell Biology, scientists discovered that before spreading to other organs, a melanoma tumor sends out tiny vesicles containing molecules of microRNA. These actions induce morphologic changes in the dermis in preparation for receiving and transporting the cancer cells. The researchers also found chemical substances that can stop the process and are therefore 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. “We have discovered how the cancer spreads to distant organs and found ways to stop the process before the metastatic stage.”

Morphologic Changes in the Dermis

The researchers began by examining pathology samples taken from melanoma patients. “We looked at samples of early melanoma, before the invasive stage,” Dr. 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.”

In the ensuing study, the group was able to discover and block a central mechanism in the metastasis of melanoma.

According to Dr. Levy, scientists have known for years that melanoma forms in the epidermis. At this early stage, the cancer is unable to send off colonizing cancer cells because it has no access to blood vessels. With no blood vessels present in the epidermis, the tumor first needs to contact the abundant blood vessels running through the dermis. But how was the connection made?

“We found that even before the cancer itself invades the dermis, it sends out tiny vesicles containing molecules of microRNA,” Dr. Levy said. “These actions induce the morphologic 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.”

Using the Mechanism

Having discovered the mechanism, the researchers proceeded to look for substances that could intervene and block the process in its earliest stages. They found two such chemicals: One (SB202190) inhibits the delivery of the vesicles from the melanoma tumor to the dermis, and the second (U0126) prevents the morphologic changes in the dermis even after the arrival of the vesicles.

Both substances were tested successfully in the lab and may serve as promising candidates for future drugs. In addition, the changes in the dermis, as well as in the vesicles themselves, can be used 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,” said Dr. Levy. “We hope that our findings will help turn melanoma into a nonthreatening, easily curable disease.”

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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