An international collaborative research team led by Dr. Nicholas Barker (Research Professor, Cancer Research Institute) at Kanazawa University has expressed a gene called "aquaporin 5 (AQP5)" in tissue stem cells responsible for the regeneration of injured stomach. I found that.As a result, we identified human gastric tissue stem cells for the first time in the world and succeeded in isolating AQP5-positive cells.We also revealed that gene mutations accumulate in these normal gastric tissue stem cells and change into gastric cancer stem cells.The research results were published in the online version of the British scientific journal "Nature" on February 2.
It is said that the reason why there is no effective therapeutic agent for malignant gastric cancer is that the tissue stem cells that can be the origin of cancer have not been identified and research on the carcinogenic mechanism has been delayed.So far, the expression of a gene called Lgr5 has been known in mouse gastric tissue stem cells, but the existence of gastric tissue stem cells in humans has been unknown.
Here, we analyzed the gene expression pattern of mouse gastrointestinal stem cells expressing the Lgr5 gene, and discovered that the cell surface protein AQP5 is characteristically expressed in the tissue stem cells of the antrum of the gastric pylorus of mice and humans.
This made it possible to isolate human AQP5-positive cells using antibodies, and succeeded in identifying human gastric tissue stem cells for the first time in the world from the verification of their cell functions.In addition, we revealed that tissue stem cells are deeply involved in the development of early gastric cancer caused by activation of the "Wnt signaling pathway" that affects various cellular processes of individual development in mice.Furthermore, it was also found that AQP5-positive gastric tissue stem cells with accumulated mutations behave as gastric cancer stem cells.
It is expected that the results of this research will dramatically deepen the understanding of the pathogenesis of human gastric cancer and gastric cancer stem cells, and will greatly contribute to the development of new therapeutic agents for gastric cancer and new therapeutic methods.
Paper information:[Nature] AQP5 enriches for stem cells and cancer origins in the distal stomach
