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H. pylori May Increase Risk of Stomach Cancer By Turning On Subset of Stem Cells – MedicalResearch.com (blog)

August 24th, 2017 1:46 am

MedicalResearch.com Interview with:Michael Sigal PhDClinical scientist of the Charit Universittsmedizin BerlinInvestigator at the Max Planck Institute for Infection Biology

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: We have previously found that H. pylori can colonize gastric glands and that in colonized glands the epithelial turnover was increased. We wanted tocharacterizethe mechanisms that control the gland turnover in thestomach.

We foundthat Axin2, a classic Wnt target gene, marks two different subpopulations of cells with stem cell properties, one of which is Lgr5-positive and theotherone Lgr5-negative. Bothpopulations are affected by Rspondin 3, that isproduced in myofibroblasts right beneath the stem cell compartment. Rspondin is crucial for stem cell signaling andknockout of Rspondin 3 in myofibroblastsresults in loss of Lgr5 and Axin2 expression. Once weincreased thebioavailability of Rspondin, that now could also interact with cells outside of the stem cellcompartment, we noticed that the number of Axin2positive stem cells dramatically increased. Of interest, only Lgr5-negative cells expanded in number and proliferate more, while the Lgr5-positive cells remained silenced.

Infection with Helicobacter pylori leads to an expansion of Axin2-positive cells which is driven by increased expression of Rspondin3. Expansion of the long lived stem cell pool could be an explanation for how H. pylori infectionincreases the risk for gastric cancer.

MedicalResearch.com: What should clinicians and patients take away from your report?

Response: It is interesting how different cell types of the tissue communicate with each other and we show an example, including the molecular details, how thiscommunication is organized and how itdynamically adapts to infection.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: I think it will be very important to address the question of how and why different subpopulations of stem cells can have differential responses to the same stimulus. What is the molecular basis for this. And also, what are the consequences?

No financial conflicts of interest.

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation:

Michael Sigal, Catriona Y. Logan, Marta Kapalczynska, Hans-Joachim Mollenkopf, Hilmar Berger, Bertram Wiedenmann, Roeland Nusse, Manuel R. Amieva, Thomas F. Meyer.Stromal R-spondin orchestrates gastric epithelial stem cells and gland homeostasis.Nature, 2017; DOI:10.1038/nature23642

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

Link:
H. pylori May Increase Risk of Stomach Cancer By Turning On Subset of Stem Cells - MedicalResearch.com (blog)

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