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Histrogical, Genetical and Protein Changes of Chief Cell in Gastric Cancer Models

胃癌模型中主细胞的组织学、遗传学和蛋白质变化

基本信息

批准号：
14370378
负责人：
KAMINISHI Michio
金额：
$ 5.5万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

项目摘要

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

除了在胃酸分泌中的作用外，壁细胞还分泌许多可能改变其他胃谱系分化的生长因子。事实上，泌酸萎缩被认为与胃腺癌风险增加最显着相关。持续幽门螺杆菌感染造成的慢性损伤会导致泌酸萎缩、小凹增生和粘液细胞化生。最近的研究描述了感染猫螺杆菌的小鼠、患有胃底为主的幽门螺杆菌胃炎的人类以及胃腺癌周围的粘膜中的 TFF2/解痉多肽表达化生 (SPEM)。该谱系的细胞再现了十二指肠布伦纳腺或深部窦腺细胞的形态，并针对三叶多肽解痉多肽（SP）（也称为 TFF2）进行免疫染色。 SPEM 与胃腺癌和泌酸萎缩的关联表明，SPEM 可能代表胃腺癌的候选前兆。我们研究了用 DMP-777 治疗胃泌素缺陷小鼠诱导的急性泌酸萎缩引起的胃粘膜谱系变化。 DMP-777 在治疗两天内引起壁细胞快速损失。泌酸萎缩伴随着 BrdU 标记的增殖细胞的快速增加以及随之而来的表面细胞数量的增加。在野生型中，治疗 7 天后，第二个祖细胞群出现在胃底腺基部，同时出现表达 TFF2/解痉多肽 (SPEM) 的粘液细胞化生。 SPEM 细胞的一个子集同时表达 TFF2 和内因子。另一方面，胃泌素缺乏的小鼠没有表现出表面细胞数量的增加，并且仅在治疗后一天就出现了 SPEM。结果表明，胃底粘膜对壁细胞的损失做出反应，诱导粘液细胞增生和粘液细胞化生，而 SPEM 的发展是对独立于胃泌素的泌酸萎缩的反应。正在研究感染幽门螺杆菌的蒙古沙鼠的胃癌模型的 SPEM。较少的

项目成果

期刊论文数量（22）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Spasmolytic polypeptide expressing metaplasia to preneoplasia in H-felis-infected mice

DOI：
10.1053/j.gastro.2004.05.029
发表时间：
2004-08-01
期刊：
GASTROENTEROLOGY
影响因子：
29.4
作者：
Nomura, S;Baxter, T;Goldenring, JR
通讯作者：
Goldenring, JR

Lee, JR, Baxter TM, Yamaguchi, H et al.: "Differential protein analysis of spasmolytic polypeptide-expressing metaplasia using laser capture microdissection and two-dimensional difference gel electrophoresis"Appl Immunohistochem Mol Morphol. 11. 188-193 (

Lee, JR, Baxter TM, Yamaguchi, H 等人：“使用激光捕获显微切割和二维差异凝胶电泳对表达解痉多肽的化生进行差异蛋白分析”Appl 免疫组织化学 Mol Morphol。

DOI：
发表时间：
期刊：
影响因子：
0
作者：
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Association of spasmolytic polyppeptide-expressing metaplasia with carcinogen adminstration and oxyntic atrophy in rats.

大鼠中表达解痉多肽的化生与致癌物质给药和泌酸萎缩的关系。

DOI：
发表时间：
2002
期刊：
Lab Invest 82
影响因子：
0
作者：
K Kogure;M Ishizaki;M Nemoto;T Shimura;K Nomoto;H Suzuki;K Kamisaka;H Kuwano;M Makuuchi;Yamaguchi H
通讯作者：
Yamaguchi H

Identification of Spasmolytic polypeptide expessing metaplasia (SPEM) in remnant gastric cancer and surveillance postgastrectomy biopsies

残余胃癌中解痉多肽表达化生 (SPEM) 的鉴定和胃切除术后活检的监测