Researchers Find Stomach Cells In Lung Tumors

Researchers have found gut cells in an unlikely spot: lung tumors. A new study from NYSCF Innovator Jay Rajagopal, MD, and colleagues at Harvard University and Duke University shows that when progenitor cells in our lungs are missing a certain gene, they instead develop into stomach, duodenum, and small intestine cells.

Tumors are composed of an eclectic cellular mixture. Cells within a single tumor can be different shapes and sizes, and they can even express different genes than their neighbors, so it isn’t surprising that not all the cells in the tumor sample looked the same. However, it was surprising to find cells in a lung tumor that are supposed to live a totally different part of the body.

The team discovered that the gut cells didn’t express a gene called NKX2-1, which typically directs progenitor cells to become a lung cell. Without that gene, the cells instead morphed into the next closest cell (developmentally speaking): gut cells.

To test make sure the absence of NKX2-1 was what was driving the cells to become gut cells, the researchers conducted an experiment in which they removed the gene from the lung tissue of mice. They noticed that the mouse’s lungs produced gut cells that even started making digestive enzymes.

Next, the team again knocked out NKX2-1, but this time activated certain oncogenes (tumor-forming genes) as well. The mice expressing the oncogenes developed tumors that resembled those typically found in the gut.

Finally, the researchers were interested in whether simply expressing or silencing genes was enough to drive cells to a certain fate, or if they needed to also exist in a specific type of environment. After generating miniature lung tumors that mimic a typical tumor’s microenvironment, the team found that manipulating genetics was enough for the progenitor cells to differentiate into gut cells.

The fact that tumors can contain different cell types demonstrates a way in which they can protect themselves from destruction. The more diverse the cells making up a tumor are, the harder it is to kill them all, since not all of the cells will respond to a drug in the same way. This study highlights this issue and stresses the importance of developing therapeutics with it in mind.

For more information on this study, check out the press release or read the paper in Developmental Cell.