セッション情報 The 2nd JSGE International Topic Conference

3)Gastric Cancer;From the View of Helicobacter pylori-related Inflammation

タイトル IT3-3:

Analysis of Gastric Stem Cell Alterations Caused by Helicobacter Infection

演者 Maeda Shin(Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Japan)
共同演者 Shibata Wataru(Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Japan)
抄録  Helicobacter-related gastritis is the major predisposing factor for gastric carcinogenesis. Recently, the cancer stem cell concept has been proposed as an attractive theory to explain cancer development. Because of similar characteristics, cancer stem cells may be derived from normal stem or stem-like cells. In order to analyze an effect of chronic inflammation on gastric stem cells and to examine a relationship between the stem cells and tumorigenesis, we used the gastric organoid culture system which can be cultured from single stem cell of mouse gastric mucosa. Mice infected with Helicobacter felis were sacrificed at 6 months post infection. Histological analysis showed severe inflammation, oxyntic atrophy, and mucous metaplasia especially in corpus. Numbers of organoids from Helicobacter-infected mucosa were significantly higher than those from uninfected control mucosa. In addition, organoid growth was more rapid in Helicobacter-infected mucosa compared to the control. mRNA expressions of stem cell markers such as CD44 and DCAMKL1 were increased in organoids cultured from Helicobacter-infected mucosa. These expressions were also confirmed by immunohitochemistry in tissue samples. We further investigated the tumorigenisity of the organoids by an implantion into immune deficient mice. After several months, organoids from Helicobacter-infected mucosa did not induce tumors, whereas tumor was generated from the organoids cultured by carcinogen MNU-injected mucosa. The current study suggests that one of the important functions of Helicobacter-induced inflammation increases the gastric stem or stem-like linage which may become an origin of cancer initiating cells. Organoid culture system and the combined xenograft model are invaluable tools for research of gastric carcinogenesis.
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