An association between the regulation of adult stem cell growth and the formation of pre-cancerous lesions has been described for the first time by researchers from the University of California-Los Angeles Jonsson Comprehensive Cancer Center. They publish their findings in the journal Stem Cell.
In lung airways, adult stem cells have the function of repairing the airways when they become damaged, for example, by smoking, pollution or a virus.
This process of repair is controlled by reactive oxygen species (ROS) molecules. Recently, other studies have shown that low levels of ROS are important for signaling stem cells to perform dividing and repairing functions, while high levels of ROS are toxic to stem cells, causing them to die.
The new study demonstrates that it is the fluctuation from low to moderate levels of ROS in the airway stem cells that triggers the repair process. Once repair is initiated, the increase in the ROS levels of the repairing cell is reduced sharply to prevent excessive cell proliferation.
Disruption to ROS reduction results in pre-cancerous lesions
However, if this natural reduction of ROS levels is disrupted, then the stem cells will continue to divide without maturing, forming instead into pre-cancerous lesions. Progressive genetic changes to the cells comprising lesions are thought to eventually allow cancerous tumors to form.
Lead author Dr. Brigitte Gomperts, associate professor in the Department of Pediatrics at the University of California-Los Angeles, explains:
Exposure to cigarette smoke, smog and bacteria can all drive the ROS levels in airway stem cells up, creating pre-cancerous lesions.
"Low ROS is what keeps stem cells in a ready state so that your body is poised and ready to respond to injury and repair. Loss of this ROS regulation leads to pre-cancerous lesions. Now, with this pre-cancerous model in place, we can begin looking for what we call driver mutations, or those specific changes that take the pre-cancerous lesions to full-blown cancer."
Dr. Gomperts and team found that exposure to cigarette smoke, smog and bacteria can all drive the ROS levels in airway stem cells up, creating pre-cancerous lesions.
Because there are several different ways in which the lesions can form, the investigators realize that the process could be different among different groups of people. As such, they believe that a personalized way of identifying disrupted pathways in patients is necessary to tailor treatment to individuals.
They suggest that high-throughput screening systems that screen large libraries of compounds will be valuable in the quest to find effective drug molecules.
Co-author and postdoctoral scholar Manash Paul describes why the team's research is so vital:
"Our study is important because it sheds light on how lung cancer can form and this will hopefully lead to new therapies for this terrible disease.
There have been studies that have looked at ROS and stem cells before, but we now know that the transition from low to high ROS levels and back down again is the true signaling message to stem cells. It is also potentially true for a number of different stem cells in the body. It solves a lot of controversy in the field."
Recently, Medical News Today reported on a study that mapped a link between smokers with a BRCA2 gene mutation and increased risk of lung cancer.
The study explained that smokers who have this mutation had a 25% chance of developing lung cancer during their lifetime. By comparison, smokers in general have a 13-15% chance of developing lung cancer.