HOUSTON: While it may appear that smoking is hazardous for your lungs, it is unknown whether and how ultrafine particles in cigarette smoke affect the development and progression of lung cancer.
Baylor College of Medicine researchers used animal models to investigate how airborne ultrafine particles in smoke can alter a host's response against lung cancer.
Dr Cheng-Yen Chang, a postdoctoral researcher in Dr Farrah Kheradmand's lab in Baylor's Department of Medicine - Pulmonary, and her colleagues revealed that exposure to ultrafine particles changes the function of immune cells in the lungs, impairing their natural defence mechanism against malignancies.
They discovered that ultrafine particles alter the fundamental energy source of the cell, resulting in novel byproducts in the lungs. The accumulation of new byproducts can weaken the host's immune response, allowing tumours to go undetected.
These particles are not just found in cigarette smoke; environmental and other natural fires also produce ultrafine particles by incompletely combusting organic debris.
Kheradmand and colleagues at Rice University previously discovered that immune cells in the lungs of heavy smokers contain nano-sized elemental carbon black particles. "When we breathe, we inhale many particles of different sizes. They are lodged somewhere along the airways, like in the nose or trachea, depending on their size."
"Ultrafine particles are so small they can navigate the respiratory system and deposit in the far distal part of the lung that is used for gas exchange - the process of breathing," Kheradmand said. "It is at that point where these particles can collect and begin to alter the way lung immune cells function."
The study illuminates how ultrafine particles promote cancer progression: Using two different mouse models of lung cancer, Chang was able to replicate the same type of exposure to ultrafine particles typically seen in a heavy smoker.
Both mouse models showed accelerated lung cancer progression when mice were exposed to nano-sized carbon black. "What we saw was that the immune cells changed what they used for energy.
They went from using fat, which is what is seen in the average cell, to using sugar. The new byproducts alter immune cells allowing for tumours to escape recognition," Chang said. "This exposure made tumours more aggressive and more likely to metastasize or spread throughout the body."
Another surprise was that whether mice were predisposed to develop cancer didn't matter; exposure to ultrafine particles still led to changes in energy usage from fat to sugar in immune cells even in the absence of any tumour.
"The particles change the powerhouse of the cells, altering their internal machinery," Kheradmand said. The study only looked at how the ultrafine particles affected immune cells and cancer development; further studies are still needed to look at other factors such as the concentration of particles and length and type of exposure.
"We are only looking at the significance of having these particles present in the airways - whether they are causing and progressing the disease. We know they have been found in smokers' lungs, so our study simulated exposure similar to a heavy smoker," Kheradmand said.
Chang and Kheradmand showed in a previous work that it is possible to make these particles more soluble so that they can be eliminated from the lungs. However, this is in lab models and is merely the first step toward a potential future cure, not a solution to make smoking safe.
"As a general rule, there is no way to make any amount of exposure safe when it comes to smoking," Kheradmand said. "The best course of action is to avoid exposure from the start."