2004 Fiscal Year Final Research Report Summary
Histrogical, Genetical and Protein Changes of Chief Cell in Gastric Cancer Models
| Project/Area Number |
14370378
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | The University of Tokyo |
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Principal Investigator |
KAMINISHI Michio the University of Tokyo, Faculty of Medicine, Professor, 医学部附属病院, 教授 (30126031)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAGUCHI Hirokazu the University of Tokyo, Faculty of Medicine, Assistant, 医学部附属病院, 助手 (00242149)
SHIMIZU Nobuyuki the University of Tokyo, Faculty of Medicine, Assistant, 医学部附属病院, 助手 (70262128)
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| Project Period (FY) |
2002 – 2004
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| Keywords | gasteic cancer / fundic mucosa / TFF2 / SPEM |
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| Research Abstract |
In addition to their role in gastric acid secretion, parietal cells secrete a number of growth factors that may alter the differentiation of other gastric lineages. Indeed, oxyntic atrophy is considered the most significant correlate with increased risk for gastric adenocarcinoma. Chronic injury in the presence of sustained H.pylori infection leads to oxyntic atrophy, foveolar hyperplasia and mucous cell metaplasia. Recent investigations have described TFF2/spasmolytic polypeptide expressing metaplasia (SPEM) in mice infected with Helicobacter felis, in humans with fundal predominant H.pylori gastritis and in the mucosa surrounding gastric adenocarcinom. The cells of this lineage recapitulate the morphology of duodenal Brunner's glands or the cells of the deep antral glands and immunostain for the trefoil polypeptide spasmolytic polypeptide (SP), also known as TFF2. The association of SPEM with gastric adenocarcinoma and oxyntic atrophy suggested that SPEM may represent a candidate pre
… More
cursor to gastric adenocarcinoma.
We studied the alterations in gastric mucosal lineages elicited by acute oxyntic atrophy induced by treatment of gastrin deficient mice with DMP-777. DMP-777 elicited rapid loss of parietal cells within two days of treatment. Oxyntic atrophy was accompanied by a rapid increase in BrdU-labeled proliferative cells and attendant increase in surface cell numbers. In wild type, after 7 days of treatment, a second progenitor population emerged at the base of fundic glands along with the development of a mucous cell metaplasia expressing TFF2/spasmolytic polypeptide (SPEM). A subset of the SPEM cells expressed both TFF2 and intrinsic factor. On the other hand, gastrin deficient mice did not demonstrate increase in surface cell numbers and SPEM emerged only one day after treatment. The results suggest that the gastric fundic mucosa responds to loss of parietal cells with induction of both mucous cell hyperplasia and mucous cell metaplasia whereas SPEM develops in response to oxyntic atrophy independent of gastrin. SPEM in H.pylori infected Mongolian Gerbil that is a gastric cancer model is being investigated. Less
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