New bio-marker for esophageal cancer

1998 Fiscal Year Final Research Report Summary

• Project/Area Number: 09671279
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Akita University
• Principal Investigator: SUZUKI Hiroyuki Akita University School of Medicine, Assistant Professor, 医学部, 講師 (10206526)
• Co-Investigator(Kenkyū-buntansha): KAMATA Syuichi Akita University School of Medicine, Research Associate, 医学部, 助手 (00224650) ; KITAMURA Michihiko Akita University School of Medicine, Associate Professor, 医学部, 助教授 (10153131)
• Project Period (FY): 1997 – 1998
• Keywords: CDDP / apoptosis / esophageal cancer / Fas / FasL / susceptibility

Research Abstract

Fas is a cell surface receptor known to trigger apoptosis when it reacts with Fas ligand (FasL) or anti Fas antibody. In this study, we examined Fas expression in six human esophageal cancer cell lines, Analysis by flow cytometry indicated that five out of six esophageal cancer cell lines expressed Fas antigen at various levels (26.2%-61.5%). Fas expression increased after CDDP treatment and the degree of increase was independent of cell sensitivity to CDDP.The anti-tumor effect of anti-Fas antibody to the esophageal cell line was enhanced by pretreatment with CDDP.Two effector systems, perforin/granzyme and FasL/Fas, are major inducers of cytotoxic lymphocytes in a model of the interaction between lymphocytes and cancer cells. The anti-tumor effect of LAK cells activated by IL-2 was enhanced by pretreatment with CDDP.In order to specifically evaluate Fas dependent cytotoxicity, LAK cells were treated with concanamycin A (CMA), which specifically inhibits perforin-dependent cytotoxicity. [AK cells expressing FasL killed only TE-2 cells (Fas positive), but not SH-1 cells (Fas negative). An anti-Fas neutralizing antibody inhibited this cytotoxicity. DNA fragmentation was shown in a cell line that was treated with CDDP and anti-Fas antibody (synergistic effect). DNA fragmentation in the target esophageal cell line was assessed using tumor cells separated from co-cultured LAK cells. TE-2 cells exhibited DNA ladder formation. Therefore, CDDP's role is not only that of a chemotherapeutic agent, but also a Fas inducer, These results suggest that apoptosis in esophageal cancer cells is controlled by CDDP and by a cytokine, such as IL-2. Therefore) a potential new therapeutic approach would therefore combine chemotherapy and immunotherapy for human malignancies.