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Bacteria Promote Cancer by Enhancing Stem Cell Replication and Turnover


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Posted 18 August 2017 - 12:25 PM


Bacterial infection has been linked to cancer risk in some cases, and here researchers propose that this is because the bacterial species can cause some stem cell populations to replicate more frequently. Greater cell activity in this fashion over time raises the risk of a cancerous mutation occurring. The authors of the study examine only the one case in which a bacteria-cancer association is well studied, but we might speculate on similar situations elsewhere in the body.

While it has long been recognized that certain viruses can cause cancer by inserting oncogenes into the host cell DNA, the fact that some bacteria can also cause cancer has been slower to emerge and much harder to prove. While it is now clear that most cases of stomach cancer are linked to chronic infections with H. pylori, the mechanism remains unknown. Researchers have spent many years investigating this bacterium and the changes it induces in the cells of the stomach epithelium. In particular, they were puzzled how malignancy could be induced in an environment in which cells are rapidly replaced.

It was suspected that the answer might lie in the stem cells found at the bottom of the glands that line the inside of the stomach, which continually replace the remaining cells 'from the bottom up' - and which are the only long-lived cells in the stomach. Researchers have now overturned the established dogma to show that H. pylori not only infects the surface cells, which are about to be sloughed off, but that some of the bacteria manage to invade deep into the glands and reach the stem cell compartment. They have now found that these stem cells do indeed respond to the infection by increasing their division - producing more cells and leading to the characteristic thickening of the mucosa observed in affected patients.

The researchers used different transgenic mice to trace cells expressing particular genes, as well as all their daughter cells. The results indicate that the stomach glands contain two different stem cell populations. Both respond to a signalling molecule called Wnt, which maintains stem cell turnover in many adult tissues. Crucially, they discovered that myofibroblast cells in the connective tissue layer directly underneath the glands produce a second stem cell driver signal, R-spondin, to which the two stem cell populations responded differently. It is this signal, which turned out to control the response to H. pylori: Following infection, the signal is ramped up, silencing the more slowly cycling stem cell population and putting the faster cycling stem cell population into overdrive.

These findings substantiate the rising awareness that chronic bacterial infections are strong promoters of cancer. 'Our findings show that an infectious bacterium can increase stem cell turnover. Since H. pylori causes life-long infections, the constant increase in stem cell divisions may be enough to explain the increased risk of carcinogenesis observed. Our new findings shed light on the intriguing ways through which chronic bacterial infections disturb tissue function and provide invaluable clues on how bacteria, in general, may increase the risk of cancer'.

Link: https://www.mpg.de/1...ylori-infection


View the full article at FightAging




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