Mesothelioma researchers at the University of Hawaii Cancer Center have found that a protein released in response to asbestos may help the rare form of cancer grow by hijacking a gene that normally works to protect the body. The study, recently published in Cell Death & Differentiation and led by Dr. Michele Carbone and Dr. Haining Yang, focuses on a protein called HMGB1 and the gene called BAP1.
Mesothelioma Begins with Asbestos Inflammation
Mesothelioma develops when asbestos fibers lodge in the cells of the thin lining around the lungs or abdomen. The fibers cause significant damage to cells, leading immune cells to release a protein called HMGB1. This protein helps the injured cells survive, and this initiates inflammation that lasts for years, eventually giving rise to cancer. In mesothelioma, cells continually produce large amounts of HMGB1 and depend on it to grow and invade nearby tissue.
The mesothelioma researchers found that HMGB1 released in response to asbestos exposure has a specific impact on BAP1, a gene that is considered a tumor suppressor. In healthy cells, BAP1 helps repair damaged DNA and keeps faulty cells from multiplying, which is why mutations in this gene increase the risk of cancer. But BAP1 also helps run routine cell functions such as growth and movement. The study showed that once a tumor has formed, the same functions that keep cells healthy can work in the aggressive cancer’s favor.
HMGB1 Accelerates BAP1 Damage in Mesothelioma
The researchers found that mesothelioma cells use the HMGB1 that results from asbestos exposure as a switch that accelerates BAP1 functions. The protein binds directly to the spot on the BAP1 gene that turns it on, fueling faster growth and metastasis. The team’s further found that mesothelioma cells lacking BAP1 grew more slowly and spread less than cells that had it, and when the team added BAP1 back, the cells became aggressive again.
Mesothelioma tumors often lose BAP1 on their own; it happens in roughly 60 percent of asbestos-related cases. Patients whose tumors have lost it tend to live about six months longer than those whose tumors still have it. The new findings suggest why: without BAP1, the asbestos-driven HMGB1 signal has nothing to amplify. The researchers suggest that mesothelioma treatment could eventually target this pathway to lower HMGB1 or BAP1 in existing tumors.
If you or someone you love has been diagnosed with mesothelioma, this type of research offers real hope for more effective treatments in the future. For more information on the resources available to you, contact the Patient Advocates at Mesothelioma.net today at 1-800-692-8608.
