Cancer skillfully disguises itself
A new study at Duke University in Durham (USA) has shown that a mutation in lung cancer cells leads to their degeneration into cells of the gastrointestinal tract.
It is known that malignant cells within the same tumor can vary greatly in structure and size. This is due to randomly occurring mutations in genes. Nevertheless, the group of researchers was surprised when cells of the stomach, duodenum and other parts of the small intestine were found in the lung tumor.
They found that these cells lacked the NKX2-1 gene, which is a kind of switch directing the development of the cell in the right direction. Without it, cells differentiate into the closest "relatives" in embryonic development – into cells of the gastrointestinal tract.
The data obtained demonstrate the flexibility of cancer cells, allowing them to survive in any conditions. It is thanks to this property that they form resistance to antitumor therapy, which is by far the most difficult problem of oncology. For example, after one course of chemotherapy, the surviving cells turn off some regulatory genes and acquire new characteristics that allow them to resist the next course of treatment.
Lung cancer is the most common cause of death among all oncological diseases and has the lowest survival rate. Non-small cell lung cancer accounts for 80-85% of all cases of this disease.
The researchers analyzed thousands of genome samples from 33 different histological types of lung cancer. They found that a large proportion of non-small cell cancer cells do not have the NKX2-1 gene, which determines differentiation into lung cells. Instead, proteins were actively synthesized, which transform into cells of the digestive system.
The cells of the respiratory and digestive systems originate from a common progenitor. That is why, according to the authors, when differentiation into the lung tissue is impaired, stomach and intestinal cells are formed.
In the experiment, mice were suppressed the NKX2-1 gene in lung tissue cells. Surprisingly, they were not only structurally reborn into cells of the gastrointestinal tract, but also performed the corresponding functions - they produced digestive enzymes.
The authors wondered whether such a genetic switch could lead to the formation of cancer cells. To get an answer to it in another experiment, they not only suppressed the NKX2-1 gene, but also activated oncogenes SOX2 or KRAS.
Mice with the SOX2 gene activated in the lungs developed forms of cancer characteristic of the upper digestive system. Activation of the KRAS gene led to the appearance of tumors in the lungs typical of the middle gastrointestinal tract.
To assess the role of the microenvironment in cell degeneration, scientists modeled the system forming around lung cancer. But it did not affect the course of the process in any way, that is, the mutation leads to structural changes regardless of the environment in which these cells are located.
Thanks to the work carried out, the mechanisms that lead to the degeneration of cancer cells and the appearance of new characteristics in them that allow them to survive during antitumor therapy have become known. The results of the study will allow us to develop new methods of treatment aimed at blocking the described process.
Article by P. R. Tata et al. Developmental History Provides a Roadmap for the Emergence of Tumor Plasticity published in the journal Developmental Cell.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru Based on Duke Today: Scientists Find Stomach Cells in Lung Cancer.