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A molecule identified by UCLA researchers helps 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.

“We think this could help us develop a new therapy that promotes airway health,” said Dr. Brigitte Gomperts, a UCLA professor of pediatrics and of pulmonary medicine, a member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA, and lead author of the study. “This could not only inform the treatment of lung cancer, but help prevent its progression in the first place.”

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.

In the new study, published today in Cell Reports, Gomperts and her colleagues 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.

Read the full story in the UCLA press release

Funding for the study was provided in part by the National Institutes of Health, the National Cancer Institute, the Tobacco Related Disease Research Program and the Broad Stem Cell Research Center Training Program, including support from the Rose Hills Foundation Graduate Scholarship. Statistical analyses were supported by UCLA CTSI grant UL1TR001881.


Image source: UCLA Broad Stem Cell Research Center/Cell Reports

Image caption: Normal airway tissue, left, and lung cancer tissue, right, with an overabundance of basal stem cells (green). The activated form of beta-catenin (red) in the lung cancer can be targeted by the Wnt Inhibitor Compound 1.