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

为了阐明整合素β4在胃癌中表达的临床意义，我们研究了在庆应义塾大学附属医院接受手术的III期或IV期胃癌患者组织中整合素β4的表达。2000年4月至今，共收集约100例患者，其中10%为整合素β4阴性肿瘤。在收集了400例患者后，我们打算前瞻性地评估整合素β4表达与临床特征之间的关系。为了阐明整合素β4在胃癌细胞中的引入机制，我们利用几种人胃癌细胞和整合素β4转染的细胞，研究了异位相关因子（Bcl-2、BAG-1和BAX）、肿瘤抑制基因（p53和Rb）和细胞生长调节因子（CDK和CDK抑制剂）的表达。结果表明，在异位诱导条件下，p21 （CDK抑制剂）在表达整合素β4的胃癌细胞中被激活，而其他因子未被激活。为了开发新的治疗胃癌腹膜转移的方法，我们利用动物模型研究了整合素β4 cDNA导入载体的作用。将整合素β4载体腹腔注射到腹膜播散的SCID小鼠后，根据腹膜结节的数量和重量评估腹膜播散的减少程度。引入整合素β4组与对照组之间无显著差异。在整合素β4诱导组，腹膜结节中未见整合素β4的表达。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。

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.