Study for usefulness of cell adhesion molecule integrin β4 in gastric cancer treatment

细胞粘附分子整合素β4在胃癌治疗中的作用研究

• 批准号: 12671262
• 负责人: FURUKAWA Toshiharu
• 金额: $ 2.5万
• 依托单位: Keio University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671262/
• 关键词: gastric cancer; peritoneal dissemination; integrin β4; apoptosis; インテグリンβ4; ヒト胃癌

To clarify the clinical significance of integrin β4 expression in gastric cancer, we have investigated the expression of integrin β4 in gastric cancer tissue of Stage III or IV patients who underwent surgery at Keio university-affiliated hospitals. From April 2000 to now, approximately 100 patients were collected and 10% of them had integrin β4-negative tumors. After 400 patients were collected, we intended to evaluate the relationship between the integrin β4 expression and clinical features prospectively.To clarify the mechanism of atoposis introduction in gastric cancer cells expressing integrin β4, we investigated the expression of atoposis-related factors (Bcl-2, BAG-1 and BAX), tumor suppressor genes (p53 and Rb) and cell growth-regulateds factors (CDK and CDK inhibitor) using several human gastric cancer cells and integrin β 4-transfected cells. As a result, p21 (CDK inhibitor) but not other factors was activated in gastric cancer cells expressing integrin β4ynder the condition of atoposis induction.To develop the new treatment of peritoneal metastasis of gastiric cancer, we investigated the effect of integrin β4 cDNA introduced-vector using animal models. After the intraperitoneal injection of integrin β4 vector into SCID mice with peritoneal dissemination, the reduction of peritoneal dissemination was evaluated on the basis of both number and weight of peritoneal nodules. There was no significant differences between the integrin β4-intoroduced group and the control group. In the integrin β4-induced group, no integrin β4 expression was observed in the peritoneal nodules. We consider that this is the reason for the negative data and are investigating the method to introduce integrin β4 vector into peritoneal nodules.

为了阐明整合素β4在胃癌中表达的临床意义，我们调查了在庆应义塾大学附属医院接受手术的III或IV期胃癌患者组织中整合素β4的表达。从2000年4月至今，收集了大约100例患者，其中10%为整合素β4阴性肿瘤。本研究收集了400例胃癌患者的临床资料，旨在前瞻性地探讨整合素β4表达与胃癌临床特征的关系，并通过对整合素β4表达的胃癌细胞中定位相关因子的表达进行研究，以阐明胃癌细胞定位的机制用整合素β 4转染的胃癌细胞系和人胃癌细胞系，检测Bcl-2、BAG-1和BAX基因、抑癌基因p53和Rb以及细胞生长调节因子CDK和CDK抑制剂的表达。结果表明，整合素β 4在胃癌细胞中表达，在异位诱导的条件下，p21（CDK抑制剂）被激活，而其他因子未被激活，为了探索胃癌腹膜转移的新治疗方法，我们采用动物模型研究了整合素β4 cDNA导入载体的作用。在腹膜内注射整合素β4载体到具有腹膜播散的SCID小鼠中后，基于腹膜结节的数量和重量来评估腹膜播散的减少。整合素β4基因导入组与对照组相比，差异无统计学意义。在整合素β4诱导组中，在腹膜结节中未观察到整合素β4表达。我们认为这是阴性数据的原因，并正在研究将整合素β4载体引入腹膜结节的方法。