In a new study, researchers found a new compound that could help maintain a healthy balance of cells in airway and lung tissue.
If the compound, so far only studied in isolated human and mouse cells, has the same effect in people, it may lead to new drugs to treat or prevent lung cancer.
The research was conducted by a team at UCLA.
Humans’ respiratory systems are constantly being injured—by pollution and germs in the air we breathe—and must be replenished with healthy cells.
That process is driven by airway basal stem cells, which divide to produce both more stem cells and the mucociliary cells that line the airways and lungs.
There are two types of mucociliary cells: mucus cells, which produce the mucus that traps toxic and infectious particles, and ciliated cells, which have finger-like projections that sweep the mucus away to keep the respiratory system healthy and clear.
In healthy lungs, airway basal stem cells stay balanced between producing mucociliary cells and self-renewing to maintain a population of stem cells.
In precancerous cells in the lungs, basal stem cells divide more often than usual, generating a large number of stem cells but too few mucociliary cells.
The resulting imbalance of cells in the airway leaves the airways unable to properly clear debris, and it creates a greater risk that the precancerous cells will give rise to a tumor.
In the new study, the team analyzed airway cells from equal numbers of biopsies of healthy people, people with premalignant lung cancer lesions and people with squamous lung cancer.
They discovered that one group of molecules—collectively called the Wnt/beta-catenin signaling pathway—was present at different levels in the basal stem cells of the patient samples versus the cells from healthy people.
And when the researchers altered the levels of these molecules in healthy airway cells from mice, the balance between stem cells and mucociliary cells shifted, mimicking the imbalance seen in lung pre-cancers.
Finally, the team screened more than 20,000 chemical compounds for their ability to reverse this effect in human cells, lowering levels of Wnt and restoring the balance of stem cells and mature airway cells.
One compound stood out for its ability to limit the proliferation of basal stem cells and restore the balance of the stem cells and mucociliary cells to normal.
The compound was also less toxic to airway cells than other, previously discovered, molecules that block Wnt/beta-catenin signaling. The team named the compound Wnt Inhibitor Compound 1, or WIC1.
The team thinks the findings could help develop a new therapy that promotes airway health. They could not only inform the treatment of lung cancer but help prevent its progression in the first place.
The compound tested by the researchers was used in preclinical tests only and has not been tested in humans or approved by the Food and Drug Administration as safe and effective for use in humans.
One author of the study is Dr. Brigitte Gomperts, a UCLA professor of pediatrics and of pulmonary medicine.
The study is published in Cell Reports.
Copyright © 2020 Knowridge Science Report. All rights reserved.
