Role of VLA-3 integrin in adhesion of cancer cells to peritoneum.

VLA-3 整合素在癌细胞粘附腹膜中的作用。

基本信息

批准号：
11672192
负责人：
TSUJI Tsutomu
金额：
$ 2.24万
依托单位：
Hoshi University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11672192/
关键词：
Integrin VLA-3 Cell adhesion Laminin Extracellular matrix Peritoneal metastasis 胃癌細胞腹膜播種

项目摘要

The adhesion of gastric cancer cells to peritoneum is a key step in the first process of peritoneal dissemination. It has been shown that various cell adhesion molecules, such as integrins, play critical roles in the adhesion. Immunohistochemical analysis of clinical specimens of gastric cancer revealed that VLA-3 (α3β1 integrin) expression is positively correlated with the peritoneal metastatic potential. This observation suggests that VLA-3 integrin may play an important role in the process of peritoneal metastasis of gastric cancer.In this study, we conducted in vitro and in vivo experiments to assess the role of VLA-3 in the adhesion of cancer cells to peritoneum. The cDNA to human α3 integrins were introduced into K562 leukemic cells, The α3 integrin-transfected cells (K3-9 cells) were found to have higher capacity in the adhesion to mouse peritoneum than the mock transfected cells (KR cells). Furthermore, the adhesion of four human gastric carcinoma cell lines to the peritoneum was partially inhibited by a monoclonal antibody against VLA-3. The expression of laminin 5 and laminin 10/11, high affinity ligands for VLA-3, was examined by the RT-PCR method. The mRNA for laminin 5 and laminin 10/11 was detected in diaphragm and peritoneum, suggesting that these members of the laminin family are involved in the VLA-3-mediated adhesion of cancer cells. In order to evaluate the contribution of VLA-3 integrin in peritoneal dissemination in vivo, K3-9 and KR cells were inoculated into the abdominal cavity of SCID mice, The formation of tumor associated with the peritoneum and diaphragm was observed three weeks after i. p. inoculation of K3-9 cells.These results strongly suggest that VLA-3 integrin mediates the initial attachment of cancer cells to peritoneum and that the overexpression of VLA-3 on cancer cells promotes the intraperitoneal tumor growth.

胃癌细胞与腹膜的粘附是腹膜播散的第一个过程的关键步骤，对胃癌临床标本的免疫组织化学分析表明，整合素等多种细胞粘附分子在粘附中发挥着关键作用。 VLA-3（α3β1 整合素）表达与腹膜转移潜能呈正相关，这一观察结果表明 VLA-3 整合素可能。在胃癌腹膜转移过程中发挥着重要作用。本研究通过体外和体内实验来评估VLA-3在癌细胞腹膜粘附中的作用，并获得了人α3整合素的cDNA。将α3整合素导入K562白血病细胞中，发现α3整合素转染细胞（K3-9细胞）比模拟细胞具有更高的小鼠腹膜粘附能力此外，抗 VLA-3 的单克隆抗体部分抑制了四种人胃癌细胞系对 VLA-3 的高亲和力配体层粘连蛋白 5 和层粘连蛋白 10/11 的表达。 3、通过RT-PCR方法检测在膈肌和腹膜中检测到层粘连蛋白5和层粘连蛋白10/11的mRNA。层粘连蛋白家族的这些成员参与了 VLA-3 介导的癌细胞粘附为了评估 VLA-3 整合素在体内腹膜传播中的贡献，将 K3-9 和 KR 细胞接种到腹腔中。 SCID 小鼠中，接种 K3-9 细胞三周后观察到与腹膜和膈肌相关的肿瘤的形成。这些结果表明 VLA-3。整合素介导癌细胞与腹膜的初始附着，并且癌细胞上VLA-3的过度表达促进腹膜内肿瘤生长。