2023 Author: Bryan Walter | [email protected]. Last modified: 2023-05-21 22:24
Immortalized epithelial cells continue to divide despite chromosomal abnormalities
Biologists from the Massachusetts Institute of Technology (USA) have traced the fate of cells with chromosomes that have incorrectly dispersed during division. These cells send pro-inflammatory signals and, with the help of special proteins on their surface, signal that they need to be killed. These signals are responded to by cells of innate immunity - natural killer cells. Probably, this mechanism allows the body to get rid of potential cancer cells in time. The research is published in the journal Developmental Cell.
Hereditary information in the somatic cells of our body is packed into 23 pairs of chromosomes. Before cell division, this set doubles, and in the process of mitosis, the chromosomes are equally divided into daughter cells. If the discrepancy fails, the daughter cells may have the wrong number of chromosomes. This phenomenon is called aneuploidy. Normally, such cells die, but several genetic syndromes are known due to aneuploidy that occurred in the early stages of embryonic development. For example, in Down syndrome, cells have an extra copy of chromosome 21. In fact, in humans, the number of such diseases can be counted on one hand, since cells strictly control all processes associated with DNA duplication, and if errors are detected, they stop the cell cycle and start a suicide (apoptosis) program.
Despite the fact that normally aneuploidy of somatic cells is a very rare event, for cancer cells it is practically a diagnostic sign. Ninety percent of tumors contain cells with extra or missing chromosomes. Often, an increase in the number of copies of some genes, along with an entire chromosome, helps cells to metastasize or acquire resistance to drugs. Genetic instability helps cancer cells evolve.
Scientists decided to find out what would happen to cells if the chromosomes were artificially prevented from separating correctly during division. In the experiment were taken "immortal" cells of the human epithelium, which can be considered a model of cancer cells. The researchers added toxins to the nutrient medium that interfere with the normal separation of chromosomes, and observed the cells using intravital microscopy.
Normal chromosome discrepancy (upper panel) and abnormal chromosome discrepancy in the presence of the cellular kinase inhibitor reversin (lower panel). One of the DNA-binding proteins in chromosomes is labeled with a red fluorescent protein.
Ninety percent of cells, despite chromosomal abnormalities, continued to divide. As a result, they formed complex karyotypes, that is, sets of chromosomes, which nevertheless successfully passed through the cell cycle. The apoptosis activation mechanism did not work for them. We can say that the researchers personally observed the evolution of cancer cells.
However, ten to fifteen percent of the cells still stopped the cell cycle and began to signal that something was wrong with them. In particular, they began to produce cytokines - signals that trigger inflammation. The researchers suggested that in response to pro-inflammatory signals, activation of innate immune cells - the so-called natural killer cells, which specialize in cancer and virus-infected cells, should occur.
To begin with, the authors checked whether the mutant cells expose any proteins by which killers can recognize them. Indeed, the number of such markers on their surface was increased. Then the authors of the work put the killers on the population of aneuploid cells and followed the fate of the latter through a microscope. It turned out that killers effectively recognize aneuploid cells and kill them (the second part of the video below, killers look like a cluster of balls). At the same time, the killers did not touch the normal cells, being in their company (the first part of the video).
Thus, the authors of the work discovered a mechanism according to which immunity cells at an early stage recognize and destroy cells that can degenerate into cancerous cells, and the latter themselves signal their state to them. However, this requires that the cells recognize the abnormality in time and stop dividing. Already reborn cells lose sensitivity to malfunctions and invent the most bizarre mechanisms to continue dividing.
Already inside a tumor, cells develop resistance to a lack of nutrients and even drugs, which they can transmit to each other using signaling molecules. We recently wrote about how this happens.