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Tumor Necrosis Factor Induces Tumor Promoting and Anti-Tumoral Effects on Pancreatic Cancer via TNFR1

Please always quote using this URN: urn:nbn:de:bvb:20-opus-97246
  • Multiple activities are ascribed to the cytokine tumor necrosis factor (TNF) in health and disease. In particular, TNF was shown to affect carcinogenesis in multiple ways. This cytokine acts via the activation of two cell surface receptors, TNFR1, which is associated with inflammation, and TNFR2, which was shown to cause anti-inflammatory signaling. We assessed the effects of TNF and its two receptors on the progression of pancreatic cancer by in vivo bioluminescence imaging in a syngeneic orthotopic tumor mouse model with Panc02 cells. MiceMultiple activities are ascribed to the cytokine tumor necrosis factor (TNF) in health and disease. In particular, TNF was shown to affect carcinogenesis in multiple ways. This cytokine acts via the activation of two cell surface receptors, TNFR1, which is associated with inflammation, and TNFR2, which was shown to cause anti-inflammatory signaling. We assessed the effects of TNF and its two receptors on the progression of pancreatic cancer by in vivo bioluminescence imaging in a syngeneic orthotopic tumor mouse model with Panc02 cells. Mice deficient for TNFR1 were unable to spontaneously reject Panc02 tumors and furthermore displayed enhanced tumor progression. In contrast, a fraction of wild type (37.5%), TNF deficient (12.5%), and TNFR2 deficient mice (22.2%) were able to fully reject the tumor within two weeks. Pancreatic tumors in TNFR1 deficient mice displayed increased vascular density, enhanced infiltration of CD4+ T cells and CD4+ forkhead box P3 (FoxP3)+ regulatory T cells (Treg) but reduced numbers of CD8+ T cells. These alterations were further accompanied by transcriptional upregulation of IL4. Thus, TNF and TNFR1 are required in pancreatic ductal carcinoma to ensure optimal CD8+ T cell-mediated immunosurveillance and tumor rejection. Exogenous systemic administration of human TNF, however, which only interacts with murine TNFR1, accelerated tumor progression. This suggests that TNFR1 has basically the capability in the Panc02 model to trigger pro-and anti-tumoral effects but the spatiotemporal availability of TNF seems to determine finally the overall outcome.show moreshow less

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Metadaten
Author: Martin Chopra, Isabell Lang, Steffen Salzmann, Christina Pachel, Sabrina Kraus, Carina A. Bäuerlein, Christian Brede, Ana-Laura Jordán Garrote, Katharina Mattenheimer, Miriam Ritz, Stefanie Schwinn, Carolin Graf, Viktoria Schäfer, Stefan Frantz, Hermann Einsele, Harald Wajant, Andreas Beilhack
URN:urn:nbn:de:bvb:20-opus-97246
Document Type:Journal article
Faculties:Medizinische Fakultät / Abteilung für Molekulare Innere Medizin (in der Medizinischen Klinik und Poliklinik II)
Medizinische Fakultät / Medizinische Klinik und Poliklinik I
Medizinische Fakultät / Medizinische Klinik und Poliklinik II
Language:English
Parent Title (English):PLoS ONE
Year of Completion:2013
Source:In: PLoS ONE (2013) 8: 9, doi:10.1371/journal.pone.0075737
DOI:https://doi.org/10.1371/journal.pone.0075737
Sonstige beteiligte Institutionen:Center for Interdisciplinary Clinical Research, Würzburg University, Würzburg, Germany
Sonstige beteiligte Institutionen:Comprehensive Heart Failure Center, Würzburg University, Würzburg, Germany
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:Bioluminescence; T cells; cancer treatment; cell staining; cytokines; immune cells; metastasis; regulatory T cells
Release Date:2014/05/07
Collections:Open-Access-Publikationsfonds / Förderzeitraum 2013
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung