Lung cancer is a leading cause of cancer deaths around the world, and is often not diagnosed until it is in late stages that are frequently untreatable. Scientists have used a mouse model to identify what they suspect is the "cell of origin" of lung squamous cell carcinoma (LUSC). This is the second most common type of lung cancer, and it tends to develop after exposure to toxins. This study has illustrated how this cell type dominates the lung environment in mice and humans affected by cancer. These cells, which are a type of basal cell in the windpipe, outcompete other cells and invade the lung. The findings, which could lead to earlier detection methods, have been reported in Science.
This work determined that these basal cells express a gene known as Krt5. Normal cells then get pushed out, as these Krt5-expressing cells expand. Cells become more and more disorganized, and lesions in the airways begin to form. This starts to create the cell structure from which LUSC develops. The expansion is so "dramatic," that entire lobes of the lung may eventually be populated by these cells, explained senior study author Professor Sam Janes of University College London (UCL).
These Krt5-expressing basal cells are the cell of origin, and this could help researchers, "design strategies to prevent lung cancer occurring in the first place or at least detect it much earlier," added Janes.
In this work, the researchers labeled cells in the trachea of mice to observe them over time. They exposed some of them to carcinogens, and monitored changes in airway cells. In the mice exposed to carcinogens, the basal cells moved into the lungs. In mice that were unexposed, the cells stayed in the trachea and did not migrate.
Different types of cells are normally balanced in the airways, but once they are exposed to carcinogens, such as tobacco smoke, the balance is disrupted. "Our experiments have shown that populations of cells originating from just a few damaged basal cells in the trachea gradually become dominant, taking over large areas of the lung," said first study author Dr. Sandra Gómez-López, also of UCL.
The researchers also assessed the genes that were active in tracheal cells in the mouse models, and cells from humans that were and are not exposed to smoke. They found that damaged basal cells grew in the airways, and transitional cells that express another gene called Krt13, also become overly abundant, while the levels of another cell type drop.
This work could help create better tests that identify lung cancer at earlier, possibly the earliest stages. This might speed treatments to affected individuals, which has the potential to significantly improve outcomes for patients. The data could also be used to develop preventive measures.
Sources: University College London, Science