In a recent study published in Nature Communications, a team of researchers from the University of Louisville described an important link associated with a major environmental cause of silicosis and a form of lung cancer.
The team led by Haribabu Bodduluri, Ph.D., researcher and professor of microbiology and immunology at the James Graham Brown Cancer Center, were able to associate the exposure of inhaled silica to a rapid progression of lung cancers. The researchers also found that an inflammatory mediator called LTB4 and its receptor BLT1 play an important role in promoting silica mediated lung tumour growth.
“We believe this is a significant step in our understanding of how environmental exposure alters the way lung cancer progresses,” Bodduluri said in a news release. “It is our hope that this new information will allow for the more rapid development of treatments for this currently incurable disease.”
Exposure to air-borne particules such as crystalline silica (CS) is a major global occupational health hazard encountered in a diverse array of industrial settings such as mining, pottery, glass and concrete production. Around two million US workers and several million more worldwide are occupationally exposed to CS particles.
“Silicosis continues to be a growing worldwide health issue. Being from Kentucky, where overall lung cancer is a major health issue, it is exciting that we may be able to develop treatments that impact people in our backyards, in addition to around the world,” Bodduluri explained.
CS exposure leads to lung infiltration of neutrophils, macrophages and lymphocytes, causing lung inflammation with the problem further enhanced by massive lung fibrosis leading to the disease silicosis, an irreversible and incurable condition due to impaired particle clearance, causing persistent lung inflammation, which can lead to lung cancer.
Epidemiological data suggest that smokers with silicosis are at even higher risk of lung cancer. Although the association of silicosis with lung cancer has been suspected for many decades, there were no established model systems to study mechanisms that link CS-induced chronic inflammation to lung cancer promotion.
In their study, the researchers observed that in mice developing spontaneous lung tumors CS exposure accelerated lung tumor progression. These results were also replicated in an implantable lung cancer model.
These findings address the relevance of silica induced leukotriene B4 mediated inflammation in lung tumor promotion. Mice lacking leukotriene B4 receptor BLT1 were protected from silica induced tumor promotion, a discovery that may facilitate development of immunotherapeutic strategies to fight silicosis and lung cancer.
Donald Miller, M.D., Ph.D., director of the James Graham Brown Cancer Center said in the news release, “This work reflects the strong commitment of the Brown Cancer Center to better understand the important role of environmental factors in causing lung cancer. Dr. Bodduluri and his team are world leaders in this field and this work may lead to novel therapies for lung cancer.”
