TRAIL Promotes Tumor Growth in a Syngeneic Murine Orthotopic Pancreatic Cancer Model and Affects the Host Immune Response. Issue 3 (March 2016)

• Record Type: Journal Article
• Authors: Beyer, Katharina; Normann, Lars; Sendler, Matthias; Käding, Andre; Heidecke, Claus-Dieter; Partecke, Lars Ivo; von Bernstorff, Wolfram
• Is Part Of: Pancreas. Volume 45:Issue 3(2016)
• Publication Date: 2016-03
• Subjects: TRAIL -- pancreatic cancer -- mice -- 6606PDA -- apoptosis -- pancreas; Pancreas -- Diseases -- Periodicals; Pancreas -- Periodicals; Neuroendocrine tumors -- Periodicals; 616.37005
• DOI: 10.1097/MPA.0000000000000469
• Languages: English
• ISSNs: 0885-3177

Abstract

Abstract : Objectives: Tumor necrosis factor (TNF)–related apoptosis-inducing ligand (TRAIL) is currently being evaluated as a possible biological agent for cancer treatment. However, many tumor cells are resistant to TRAIL-induced apoptosis. In these cases, TRAIL may activate different pathways promoting tumor growth as well as showing different interactions with the immunological tumor microenvironment. In this study, the impact of TRAIL on tumor growth and survival in a syngeneic model of TRAIL-resistant pancreatic cancer cells was investigated. Methods: Murine 6606PDA pancreatic cancer cells were injected into the pancreatic heads of TRAIL −/− − mice and their littermates. To examine a direct effect of TRAIL on tumor cells, cultures of 6606PDA were TRAIL stimulated. Results: The TRAIL −/− − mice displayed significantly decreased tumor volumes and an enhanced overall survival in pancreatic cancer. The decreased tumor growth in TRAIL −/− − mice was accompanied by a decrease of regulatory CD4 cells within tumors. Concordantly, TRAIL treatment of wild-type mice enhanced tumor growth and increased the fraction of regulatory CD4 cells. Yet, a direct effect of TRAIL on 6606PDA cells was not detected. Conclusions: Thus, TRAIL can promote tumor growth in TRAIL-resistant tumor cells. This may restrict possible future clinical applications of TRAIL in pancreatic cancer.