Mesothelioma Research May Benefit From Discovery That Silences Metastasis

• Nancy Meredith
• Featured News

Mesothelioma cancer cells thrive by splitting and dividing, resulting in metastasis of the cancer to other organs. Stopping tumor growth and preventing metastasis, especially in mesothelioma and lung cancer that are both highly aggressive and resistant to many cancer treatments, is critical for increasing survival in patients. Now, researchers report they have found a key molecule in lung cancer cells that can halt metastasis.

Researchers at Imperial College London report, in a March 21 press release, the MARK4 protein enables cancer cells to split off from its tumor of origin and move to other parts of the body. However, they also found that the miR-515-5p molecule interferes with the production of MARK4. In effect, the molecule “silences” the production of MARK4, preventing the cancer cells from migrating.

http://www3.imperial.ac.uk/newsandeventspggrp/imperialcollege/newssummary/news_21-3-2016-14-56-5

“The ability of a cancer to spread around the body has a large impact on a patient’s survival,” said Professor Justin Stebbing, senior author of the study from the Department of Surgery and Cancer  at Imperial. “However, at the moment we are still in the dark about why some cancers spread around the body – while others stay in one place. This study has given important insights into this process.”

It is cancer metastasis, and not the original cancer diagnosis itself, that is the cause of nearly all cancer deaths. In fact, according to various studies, 90 percent of all cancer deaths are due to metastasis. The American Cancer Society reports lung cancer can spread to almost any organ of the body, but most often it will spread to the adrenal glands, liver, bones, or brain. It can also spread to the other lung.

The Imperial College researchers looked at breast and lung cancers and found that reduced miR-515-5p and increased MARK4 levels in both of the cancers correlated to poor patient prognosis. They then increased the amount of miR-515-5p in mouse models using human breast cancer and lung cancer cells and found the higher level of the molecule prevented the spread of cancer cells.

The researchers next step is to assess if the MARK4 protein or the silencer molecule (miR-515-5p) should be anti-cancer drug targets. In addition, the team is investigating whether developing a test for the miR-515-5p molecule could provide a tool to indicate the likelihood of metastasis.

“These findings could have profound implications for treating breast and lung cancers, two of the biggest cancer killers worldwide,” said Dr. Olivier Pardo, lead author of the paper, also from the Department of Surgery and Cancer at Imperial.

Mesothelioma, a rare form of cancer caused by exposure to airborne asbestos fibers, can spread throughout the body by entering the blood stream or the lymphatic system. Due to the aggressive nature of the cancer, it is rare that mesothelioma cells remain confined to the site of origin and have not invaded neighboring tissue through metastasis. Research of this type brings hope to the mesothelioma community that new, effective treatments will soon be available.

See the Feb. 10 issue of the journal EMBO Reports for the full results of the study.

http://onlinelibrary.wiley.com/doi/10.15252/embr.201540970/suppinfo