Are stem cells the link between bacteria and cancer?

August 17, 2017
Cross section of stomach glands, showing the outline of individual cells in green and their nuclei in blue. Credit: MPI for Infection Biology

Gastric carcinoma is one of the most common causes of cancer-related deaths, primarily because most patients present at an advanced stage of the disease. The main cause of this cancer is the bacterium Helicobacter pylori, which chronically infects around half of all humans. However, unlike tumour viruses, bacteria do not deposit transforming genes in their host cells and how they are able to cause cancer has so far remained a mystery. An interdisciplinary research team at the Max Planck Institute in Berlin in collaboration with researchers in Stanford, California, has now discovered that the bacterium sends stem cell renewal in the stomach into overdrive – and stem cell turnover has been suspected by many scientists to play a role in the development of cancer. By showing that the stomach contains two different stem cell types, which respond differently to the same driver signal, they have uncovered a new mechanism of tissue plasticity. It allows tuning tissue renewal in response to bacterial infection.

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 cancer are linked to chronic infections with H. pylori, the mechanism remains unknown.

Thomas F. Meyer and his colleagues at the Max Planck Institute for Infection Biology in Berlin have spent many years investigating this bacterium and the changes it induces in the of the stomach epithelium. In particular, they were puzzled how malignancy could be induced in an environment in which cells are rapidly replaced. They suspected that the answer might lie in the 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. Michael Sigal, a clinical scientist of the Charité – Universitätsmedizin Berlin, who joined the Max Planck team, 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.

They used different transgenic mice to trace cells expressing particular genes, as well as all their daughter cells. The results, published in Nature 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 , 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', says Sigal. '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,' and Meyer adds: 'Our new findings shed light on the intriguing ways through which disturb tissue function and provide invaluable clues on how bacteria, in general, may increase the risk of '.

Explore further: ONC201 may inhibit cancer stem cell self-renewals by altering their gene expression

More information: Michael Sigal et al. Stromal R-spondin orchestrates gastric epithelial stem cells and gland homeostasis, Nature (2017). DOI: 10.1038/nature23642

Related Stories

ONC201 may inhibit cancer stem cell self-renewals by altering their gene expression

August 2, 2017
ONC201 may inhibit cancer stem cell self-renewals by altering their gene expression, according to a study published August 2, 2017 in the open-access journal PLOS ONE by Varun Vijay Prabhu from Oncoceutics, Inc., USA and ...

Ulcer-causing bacteria induces stomach stem cell growth in mice, researchers find

May 6, 2015
The ulcer-causing bacterium Helicobacter pylori can directly interact with stomach stem cells, causing the cells to divide more rapidly, according to a new study by researchers at the Stanford University School of Medicine.

Helicobacter pylori causes gene activity in the gastric cells resembling the activity of cancer cells

June 12, 2015
Around half of the global population is chronically infected with the stomach bacterium Helicobacter pylori, almost 1% of whom go on to develop gastric adenocarcinoma, one of the deadliest forms of cancer. Usually it takes ...

Stomach bacterium damages human DNA

September 6, 2011
The stomach bacterium Helicobacter pylori is one of the biggest risk factors for the development of gastric cancer, the third most common cause of cancer-related deaths in the world. Molecular biologists from the University ...

Recommended for you

Researchers develop treatment to reduce rate of cleft palate relapse complication

September 22, 2017
Young people with cleft palate may one day face fewer painful surgeries and spend less time undergoing uncomfortable orthodontic treatments thanks to a new therapy developed by researchers from the UCLA School of Dentistry. ...

Exosomes are the missing link to insulin resistance in diabetes

September 21, 2017
Chronic tissue inflammation resulting from obesity is an underlying cause of insulin resistance and type 2 diabetes. But the mechanism by which this occurs has remained cloaked, until now.

Thousands of new microbial communities identified in human body

September 20, 2017
A new study of the human microbiome—the trillions of microbial organisms that live on and within our bodies—has analyzed thousands of new measurements of microbial communities from the gut, skin, mouth, and vaginal microbiome, ...

Study finds immune system is critical to regeneration

September 20, 2017
The answer to regenerative medicine's most compelling question—why some organisms can regenerate major body parts such as hearts and limbs while others, such as humans, cannot—may lie with the body's innate immune system, ...

Immune cells produce wound healing factor, could lead to new IBD treatment

September 20, 2017
Specific immune cells have the ability to produce a healing factor that can promote wound repair in the intestine, a finding that could lead to new, potential therapeutic treatments for inflammatory bowel disease (IBD), according ...

As men's weight rises, sperm health may fall

September 20, 2017
(HealthDay)—A widening waistline may make for shrinking numbers of sperm, new research suggests.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.