The mechanism of destruction of precancerous cells is revealed
Denis Strigun, Naked Science
Experts from the Massachusetts Institute of Technology and the University of California at San Diego have clarified the mechanism of cell destruction in aneuploidy.
Normally, the human genome consists of 23 pairs of chromosomes. During mitosis, these structures are bifurcated and equally diverge between daughter cells. Failure at this stage leads to aneuploidy – a change in the karyotype, in which the number of chromosomes is not multiple to the haploid (with a single copy of the chromosome) set. Such a violation can lead to spontaneous abortions and hereditary syndromes, for example, Down syndrome, which is characterized by the presence of an extra copy of the 21st chromosome. In addition, genetic defects are characteristic of many malignant, especially solid, tumors. Thus, variations in the number of copies of genes are often associated with an increase in their resistance and metastasis.
However, such genetic instability is relatively rare. It is known that when chromosome segregation is violated, the proliferation of defective cells is suspended and the process of apoptosis is started. The exact mechanism of the immune response in this case has so far remained unclear. To fill the gap, American biologists conducted a series of experiments.
Details of the study are presented in the journal Developmental Cell (Santaguida et al., Chromosome Mis-segregation Generates Cell-Cycle-Arrested Cells with Complex Karyotypes that Are Eliminated by the Immune System).
At the first stage, they grew "immortal" retinal pigment epithelial cells hTERT (can serve as a cancer model) in the presence of toxins and observed anomalies of chromosome divergence during division. The analysis showed that 80 percent of these cells continued to proliferate, despite the defects that occurred.
As a result, model cells formed complex karyotypes with aneuploidy in the absence of apoptosis. Meanwhile, about nine percent of cells stopped dividing and began to produce cytokines – informational molecules mediating intercellular signaling, including during apoptosis. Scientists have suggested that the production of these compounds can provoke the activity of natural killers. They are large granular lymphocytes that are cytotoxic to cancer and infected cells. The hypothesis was confirmed: the damaged cells exhibited an increased number of specific biomarkers (MICA and MICB) for binding to lymphocytes.
A diagram from an article in the Developmental Cell – VM.
The researchers then mixed natural killer cells with defective cells. According to the results, after 6-12 hours, lymphocytes began to destroy aneuploid cells, while not affecting cells with a full set of chromosomes. According to the authors, the data obtained clarify the mechanism of recognition and utilization of cancer cells at an early stage. It is noteworthy that the damaged biomaterial independently signaled mutations (via the NKG2D receptor on the lymphocyte membrane), but most of these cells did not bind to killers. An additional experiment to inhibit the NKG2D receptor confirmed that such antigens prevent apoptosis.
Portal "Eternal youth" http://vechnayamolodost.ru
21.06.2017