Asbestos Causes Mesothelioma Through Release of This Protein, Study Finds

Some of the world’s top mesothelioma experts believe they now have a better understanding of how asbestos causes mesothelioma. The finding could help lead to more effective ways of treating it. 

Malignant mesothelioma is a deadly cancer caused by exposure to asbestos. There is no cure. Once symptoms develop, many patients do not live beyond a year. 

Scientists have known since the early 1900s that asbestos causes mesothelioma. But they are still trying to figure out exactly how. A new international study led by the University of Hawaii may help answer the question.

Membrane Cells Under Attack

Mesothelioma is a cancer of a mesothelial membrane. The most common mesothelial membrane where mesothelioma occurs is the pleura. The pleura is a multi-later membrane surrounding the lungs. 

Exposure to asbestos causes mesothelioma tumors on the pleura. As pleural mesothelioma spreads, the membrane becomes stiff and unyielding. This makes it harder for patients to get a deep breath. Over time, mesothelioma cells may spread to other parts of the body and seed new tumors.

The fact that asbestos causes mesothelioma does not make total sense. Scientists know that asbestos is lethal to mesothelial cells. Many of these cells die when they encounter asbestos. 

But this does not happen to all asbestos-exposed mesothelial cells. Some mesothelial cells survive and turn into cancer cells. The new study focused on why this happens. 

HMGB1 Helps Explain How Asbestos Causes Mesothelioma

Autophagy is the body’s way of preserving the usable parts of damaged cells. It is an alternative to killing the cells. With autophagy, the good parts can be re-used to make new, stronger cells. When it happens in cancer cells, autophagy can help tumors survive and grow.  

The new research found that one way asbestos causes mesothelioma may be through higher rates of autophagy. The reason may be a protein called HMGB1.

“We discovered that the release of HMGB1 upon asbestos exposure promoted autophagy, allowing a higher fraction of HM [mesothelial cells] to survive asbestos exposure,” write the authors. 

Asbestos triggers HMGB1 which may help damaged mesothelial cells survive. These cells can then go on to turn into mesothelioma tumors. 

To test the theory, the researchers used mice that could not produce HMGB1. They called them HMGB1-cKO mice. They exposed mesothelial cells from these mice to asbestos. 

Compared to unaltered mice, “mesothelial cells from HMGB1-cKO mice showed significantly reduced autophagy and increased cell death,” the authors report. 

Understanding how asbestos causes mesothelioma could lead to new ways of treating or even preventing it. Tens of thousands of people have been exposed to asbestos. Right now, there is no way to keep them from getting mesothelioma. There is also no way to predict who will get it. 

Sources:

Xue, J, et al, “Asbestos induces mesothelial cell transformation via HMGB1-driven autophagy”, September 30, 2020, Proceedings of the National Academy of Sciences, Epub ahead of print, https://www.pnas.org/content/early/2020/09/29/2007622117