Don 't wake up famously
Dormant cancer cells wake up from inflammation
Kirill Stasevich, "Science and Life"
Even after successful removal and treatment of cancer, dormant cells may remain in the body after it – having broken away from the tumor, they simply exist, not manifesting themselves in any way and not dividing; this can be called canned metastases. But if they wake up, a person will have a new tumor. The question arises, what can wake up such cells.
Researchers from the Cold Spring Harbor Laboratory write in Science that, at least in some cases, an inflammatory reaction serves as a wake-up call; that is, roughly speaking, sleeping cancer cells awaken the immune system, because the immune system is in charge of inflammation.
The experiments were performed on rats in which tumor cells remained after breast and prostate tumors. These cells reached the lungs and woke up – that is, they began to divide – when inflammation was provoked in the lungs. Separately, it should be clarified that the inflammation in the lungs was triggered either by pieces of bacterial cells (that is, simulating an infection), or by tobacco smoke; the rats, of course, did not smoke, they were simply kept in an unhealthy smoky atmosphere.
But inflammation is too complex a process with many participants. What kind of inflammatory molecules and what kind of immune cells cause cancer cells to wake up? It turned out that everything starts with neutrophils, or neutrophil granulocytes. Neutrophils are among the first to encounter foreign particles, be it bacteria or something else, and literally eat them. Bacterial cells die from a variety of immune proteins, but neutrophils themselves also die, releasing new portions of antibacterial substances and at the same time sending chemical signals that attract other immune cells to the "battleground".
However, chemical signals and antibacterial enzymes are not everything. Neutrophils use a rather strange weapon: a trap net hung with bactericidal proteins. We wrote about how it turns out: neutrophils release a strand of DNA from themselves, fix it on the surface and then crawl away, like some spider weaving a web. Other neutrophils that stumble upon DNA also begin to "weave a network", so that even a small number of cells can "weave" as a result a relatively large space. Bactericidal proteins that sit on DNA strands kill bacteria trapped in the network.
Photo by Park et al., Science Translational Medicine, 2016.
It was such networks that neutrophils made in the lungs during inflammation. Two enzymes that sit on the network make incisions in the laminin protein molecule, which is located in the intercellular space. Laminins serve as physical support for tissue, they help cells attach, move, transmit signals to each other, etc. But after the enzymes of the neutrophil DNA network cut laminin, its molecule changes shape. A sleeping cancer cell discovers that laminin has changed shape, and this serves as a wake–up signal - the cell decides that it's time for it to start dividing. If you cover those places in the laminin molecules that wake up the cancer cell, then it will not wake up, and no metastatic tumor will appear.
Earlier, Mikala Egeblad and her colleagues from the Cold Spring Harbor Laboratory published an article in Science Translational Medicine that the same immune DNA networks help cancer metastasize - malignant cells next to the networks are particularly easy to penetrate into healthy tissues. Perhaps if we manage to find a means that will destroy neutrophil networks in a timely and effective manner, this will make cancer metastases less dangerous.
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