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

2001 Fiscal Year Final Research Report Summary

• Project/Area Number: 12671262
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Keio University
• Principal Investigator: FURUKAWA Toshiharu Keio University, Med., Instructor, 医学部, 助手 (60219102)
• Co-Investigator(Kenkyū-buntansha): KITAJIMA Masaki Keio University, Med., Professor, 医学部, 教授 (90112672) ; KUBOTA Tetsuro Keio University, Med., Associate Professor, 医学部, 助教授 (00118944) ; WATANABE Masahiko Keio University, Med., Assistant Professor, 医学部, 講師 (80146604)
• Project Period (FY): 2000 – 2001
• Keywords: gastric cancer / peritoneal dissemination / integrin β4 / apoptosis

Research Abstract

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.