Function of TRAIL for immune evasion in colon cancers

2003 Fiscal Year Final Research Report Summary

• Project/Area Number: 14570460
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Mie University
• Principal Investigator: SHIRAKI Katsuya Mie University, University Hospital, Assistant Professor, 医学部附属病院, 講師 (90263003)
• Co-Investigator(Kenkyū-buntansha): MURATA Kazumoto Mie University, Faculty of Medicine, Research Associate, 医学部, 助手 (40345971) ; MURATA Kazumoto Mie University, Faculty of Medicine, Research Associate (40345971) ; MURATA Kazumoto Mie University, Faculty of Medicine, Research Associate (40345971) ; MURATA Kazumoto Mie University, Faculty of Medicine, Research Associate (40345971) ; MURATA Kazumoto Mie University, Faculty of Medicine, Research Associate (40345971)
• Project Period (FY): 2002 – 2003
• Keywords: TRAIL / Colon Cancer / Immune Evasion / apoptosis

Research Abstract

TNF-related apoptosis-inducing ligand (TRAIL) can induce apoptosis in various transformed cell lines. Therefore we investigated TRAIL sensitivity, TRAIL-induced NF-xB activation, and the expression of TRAIL in human colonic adenocarcinoma cell lines (HT 29, LS180, SK-CO-1). All four TRAIL receptors (TRAIL-RI-R4) are expressed in these cell lines. TRAIL sensitivity was assessed by assay of cell viability. Cancer cell viabilities were 83±3.1% (HT-29), 90±4.3% (LS180) and 88±6.3% (SK-CO-1) at 24 hours after the addition of 100ng/ml TRAIL, indicating that these cell lines were relatively resistant to TRAIL. Activation of NF-xB was variably influenced by TRAIL administration, with no consistent tendency among the cell lines, indicating that TRAIL-induced NF-xB activation might be cell-type dependent. In contrast, TRAIL was expressed in the human colonic adenocarcinoma cell lines by western blotting and RT-PCR. Increased expression of TRAIL on tumor cells were observed by flow cytometry after cytokine stimulation (IFNγ, TNFα) or the addition of chemotherapeutic agents (camptothecin, doxolubicin hydrochloride). The TRAIL on HT-29 cells was functional and able to induce apoptosis in Jurkat cells. The Jurkat cell viability increased by addition of TRAILR1-R4-Fc. In the presence of various cytokines or existence of chemotherapeutic agents, functional TRAIL is expressed on the surface of tumor cells, and this expressed TRAIL might contribute to tumor immune privilege by inducing apoptosis of activated human lymphocytes.