Scientists say they have identified the mechanism that explains how fine air pollution particles might cause lung cancer.

The team from the Nanjing University (NJU), Nanjing, China, and the University of Macau say the findings could lead to new approaches for preventing or treating the initial lung changes that lead to the disease.

The World Health Organisation (WHO) have identified air pollution as one of the world’s biggest killers. In its latest Global Air Quality Guidelines issued last September the WHO said poor air quality is killing millions across the world.

“Every year, exposure to air pollution is estimated to cause 7 million premature deaths and result in the loss of millions more healthy years of life,” it stated. “In children, this could include reduced lung growth and function, respiratory infections and aggravated asthma. In adults, ischaemic heart disease and stroke are the most common causes of premature death attributable to outdoor air pollution, and evidence is also emerging of other effects such as diabetes and neurodegenerative conditions. This puts the burden of disease attributable to air pollution on a par with other major global health risks such as unhealthy diet and tobacco smoking.”

The report added: “Air pollution is one of the biggest environmental threats to human health, alongside climate change. Improving air quality can enhance climate change mitigation efforts, while reducing emissions will in turn improve air quality. By striving to achieve these guideline levels, countries will be both protecting health as well as mitigating global climate change.”

The researchers said tiny, inhalable fine particulate matter (FPM) found in air pollutants has been recognised as a Group 1 carcinogen and a substantial threat to global health. However, the cancer-causing mechanism of FPM remains unclear.

“Despite its potential to cause mutations, recent research suggests that FPM does not directly promote, and may even inhibit, the growth of lung cancer cells,” explained first author Zhenzhen Wang, an associate researcher at Nanjing University. “This suggests that FPM might lead to cancer through indirect means that support tumour growth. For example, some studies suggest FPM can prevent immune cells from moving to where they are needed.”

To explore this issue, Wang and the team collected FPM from seven locations in China and studied its effects on the main immune cells that defend against tumour growth, called cytotoxic T-cells (CTLs). In mice administered with lung cancer cells that were not exposed to FPM, CTLs were recruited to the lung to destroy the tumour cells. By contrast, in the mice whose lungs were exposed to FPM, the infiltration of CTLs was delayed – potentially allowing the tumour cells to establish in lung tissue.

To investigate why the CTLs did not enter the lung as quickly in the FPM-exposed lungs, the team studied both the CTLs themselves and the lung tissue structure. They found that CTLs exposed to FPM still retained their migratory ability, but that FPM exposure dramatically compressed the lung tissue structure and the spaces that immune cells move between. There were also much higher levels of collagen, a protein that provides biomechanical support for cells and tissues. When the team studied the movement of CTLs in the mice, in lung tissue exposed to FPM, CTLs struggled to move, whereas those in the untreated tissue were able to move freely.

Further analysis of the tissue showed that the structural changes were caused by increases in a collagen subtype called collagen IV, but the team still did not know how FPM triggered this. They found the answer when they looked more closely at the structural changes to collagen IV and the enzyme responsible for making them, called peroxidasin. This enzyme drives a specific type of cross-linking that exposure to FPM was found to cause and aggravate in the lung tissue.

“The most surprising find was the mechanism by which this process occurred,” Wang said. “The peroxidasin enzyme stuck to the FPM in the lung, which increased its activity. Taken together, this means that wherever FPM lands in the lung, increased peroxidasin activity leads to structural changes in the lung tissue that can keep immune cells out and away from growing tumour cells.”

“Our study reveals a completely new mechanism by which inhaled fine particles promote lung tumour development,” concludes senior author Lei Dong, professor at the School of Life Sciences, Nanjing University. “We provide direct evidence that proteins that stick to fine particulate matter can cause a significant and adverse effect, giving rise to pathogenic activity. Our discovery that peroxidasin is the mediator of this effect in lung tissue identifies it as a specific and unexpected target for preventing lung disease caused by air pollution.”

The World Health Organisation (WHO) have identified air pollution as one of the world’s biggest killers. In its latest Global Air Quality Guidelines issued last September the WHO said poor air quality is killing millions across the world.

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