Production of monoclonal antibody against liver metastasis from cancer of human digestive organ and its clinical application.

1994 Fiscal Year Final Research Report Summary

• Project/Area Number: 05671041
• Research Category: Grant-in-Aid for General Scientific Research (C)
• Allocation Type: Single-year Grants
• Research Field: Digestive surgery
• Research Institution: Akita University
• Principal Investigator: KOTANAGI Hitoshi Akita University, School of Medicine, Assistant, 医学部, 助手 (00161935)
• Co-Investigator(Kenkyū-buntansha): TANAKA Junichi Akita University, School of Medicine, Assistant, 医学部, 助手 (30171763)
• Project Period (FY): 1993 – 1994
• Keywords: Colon cancer / Liver metastasis / Monoclonal antibody / Cell surface antigen / Adhesion molecules

Research Abstract

The aim of this study is to clarify the mechanisms of liver metastasis from cancer of digestive organs after producing monoclonal antibodies specific for liver metastasis and use these antibodies to the diagnosis and therapy of liver metastasis. Cancer cells within liver metastasis are considered to have all characters essential to liver metastasis. Therefore, monoclonal antibody was produced by cell fusion methods between myeloma cells and splenocytes which were immunized by cells within liver metastasis from human colon cancer. Furthermore, colon cancer cell lines with high potential of liver metastasis were established to investigate changes of cell surface antigens in the course of getting high metastatic potential, and to use them as an antigen for production of monoclonal antibody specific for cells with high metastatic potential.
Two monoclonal antibodies arised against cells within liver metastasis reacted relatively specific to colon cancer and liver metastasis tissue, inhibited cell adhesion between colon cancer cells and hepatocytes, and recognized different adhesion molecules from these reported previously. Two cance cell lines with high potential of liver metastasis were selected by repeated injection of cells within liver metastasis to the spleen of SCID mouse. Though the expression of receptors of growth factors and glycoproteins at the cell surface did not change as cells getting high metastatic potential, the expression of adhesion molecules, such as CEA and sialyl Le^a, increased significantly. The production of monoclonal antibody was tried using cells with high metastatic potential as an antigen to detect new antigens specific for liver metastasis. But, we can not yet establish such antibodies.
From these studies, it is emphasized that adhesion molecules play an important role in the mechanisms of liver metastasis. The clinical application of monoclonal antibodies specific for liver metastasis will be performed in the future study.