Researchers from Duke University have discovered a miniature digestive system inside a lung tumor. The team was surprised to see a mini stomach, duodenum and even small intestine hidden away in this cancer sample.
As reported in the journal Development Cell, the researchers discovered that the cancerous cells lost a gene called NKX2-1. This gene acts like a master switch, telling lung cells how to develop and it appears that without it, cells begin to develop like the gut. This incredible ability to change gives cancer another redoubtable way to fight off treatments.
“Cancer cells will do whatever it takes to survive,” lead author Professor Purushothama Rao Tata said in a statement. “Upon treatment with chemotherapy, lung cells shut down some of the key cell regulators and pick up the characteristics of other cells in order to gain resistance.”
Tata and his colleagues looked at “non-small cell lung cancer” using the extensive database of the Cancer Genome Atlas Research Network. The team was able to sift through thousands of cancer genome and they discovered that a large proportion of non-small cell lung cancer lacked that specific gene.
Since both lungs and gut cells come from the same progenitor cells, the researchers proposed that the lack of NKX2-1 would allow them to take on a different developmental path. And this means cancer gut cells would be able to escape treatment because they wouldn’t be affected by attacks on lung cells.
The team tested this idea in mouse models by removing the NKX2-1 gene in question from the lung tissue. The mice lung cells started creating features that usually only appear in the gut, such as gastric tissue. Surprisingly, they even started producing digestive enzymes. When tumors were induced, they looked as they belonged in the foregut. Wondering whether any other signals were needed to alter the state of lung cells, the researchers created a mini lung tumor system and found that simply manipulating genes was enough for lung tumors to begin mutating.
“Cancer biologists have long suspected that cancer cells could shapeshift in order to evade chemotherapy and acquire resistance, but they didn’t know the mechanisms behind such plasticity,” said Tata. “Now that we know what we are dealing with in these tumors – we can think ahead to the possible paths these cells might take and design therapies to block them.”
Non-small cell lung cancer accounts for 80 to 85 percent of all lung cancer cases and lung cancer is the leading cause of cancer death worldwide. Over 230,000 people will be diagnosed with lung cancer in the US in 2018 and over 150,000 will die of it.