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The Role of TNF in Cancer

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Death Receptors and Cognate Ligands in Cancer

Part of the book series: Results and Problems in Cell Differentiation ((RESULTS,volume 49))

Abstract

Tumor necrosis factor (TNF) is an extraordinarily pleiotropic cytokine with a central role in immune homeostasis, inflammation, and host defense. Dependent on the cellular context, it can induce such diverse effects as apoptosis, necrosis, angiogenesis, immune cell activation, differentiation, and cell migration. These processes are of great relevance in tumor immune surveillance, and also play crucial roles in tumor development and tumor progression. It is therefore no surprise that TNF in a context-dependent manner displays pro- and antitumoral effects. Modulation of the activity of the TNF–TNF receptor system thus offers manifold possibilities for cancer therapy. In fact, TNF in combination with melphalan is already an established treatment option in the therapy of advanced soft tissue sarcoma of the extremities and many preclinical data suggest that TNF neutralization could also be exploited to fight cancer or cancer-associated complications.

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Abbreviations

AOM:

Azoxymethane

APC:

Antigen presenting cell

COX-2:

Cyclo-oxygenase-2

cIAP1/2:

Cellular inhibitor of apoptosis protein-1/2

DMBA:

7,12-di-methylbenz[α]-anthracene

DSS:

Dextran sulfate sodium salt

EMT:

Epithelial–mesenchymal transition

ERK:

Extracellular-regulated kinase

FADD:

Fas-associated death domain

GSK3β:

Glycogen synthase kinase

ILP:

Isolated limb perfusion

JNK:

cJun N-terminal kinase

LMCV:

Lymphocytic choriomeningitis virus

MCA:

3′-Methylcholanthrene

MCP1:

Monocyte chemoattractant protein-1

MDR2:

Multidrug resistance p-glycoprotein 2

MMP-9:

Matrix metalloprotease-9

OA:

Ocadaic acid

PDAC:

Pancreatic ductal adenocarcinoma

p38 MAPK:

p38 mitogen-activated protein (MAP) kinase

RANK:

Receptor activator of NF-kappaB

TPA:

12-0-Tetradecanoyl-phorbol-13-acetate

TRPV1:

Transient receptor potential channel vanilloid type 1

VEGFR2:

Vascular endothelial growth factor (VEGF) receptor

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Authors and Affiliations

  1. Department of Molecular Medicine, Medical Clinic and Polyclinic II, University of Würzburg, Röntgenring 11, 97070, Wuerzburg, Germany

    Harald Wajant

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  1. Harald Wajant
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Correspondence to Harald Wajant .

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  1. Klinik für Allgemeine Chirurgie und, Universitätsklinikum Schleswig-Holstein, Arnold-Heller-Str. 7, Kiel, 24105, Germany

    Holger Kalthoff

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Wajant, H. (2009). The Role of TNF in Cancer. In: Kalthoff, H. (eds) Death Receptors and Cognate Ligands in Cancer. Results and Problems in Cell Differentiation, vol 49. Springer, Berlin, Heidelberg. https://doi.org/10.1007/400_2008_26

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