Influence of TBK-1 on tumor angiogenesis and microvascular inflammation

Tank-Binding-Kinase 1 (TBK-1) has been proposed as a putative mediator in tumor angiogenesis. It was the aim of our study to gain insight into TBK-1s role in tumor angiogenesis and tumor-associated microvascular inflammation. TBK-1 overexpressing KB 3-1 cells were generated and their growth characte...

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Published inFrontiers in bioscience Vol. 13; no. 13; pp. 7243 - 7249
Main Authors Czabanka, Marcus, Korherr, Christian, Brinkmann, Ulrich, Vajkoczy, Peter
Format Journal Article
LanguageEnglish
Published United States 01.05.2008
Subjects
Animals
Antineoplastic Agents - therapeutic use
Chemokine CCL5 - physiology
Clone Cells
Humans
Inflammation - physiopathology
Inflammation - prevention & control
Interleukin-8 - physiology
KB Cells
Male
Mice
Mice, Nude
Microcirculation - pathology
Neoplasms - drug therapy
Neoplasms - enzymology
Neoplasms - genetics
Neovascularization, Pathologic
Polymerase Chain Reaction
Protein-Serine-Threonine Kinases - genetics
Protein-Serine-Threonine Kinases - metabolism
Vascular Endothelial Growth Factor A - physiology
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Summary:Tank-Binding-Kinase 1 (TBK-1) has been proposed as a putative mediator in tumor angiogenesis. It was the aim of our study to gain insight into TBK-1s role in tumor angiogenesis and tumor-associated microvascular inflammation. TBK-1 overexpressing KB 3-1 cells were generated and their growth characteristics were analyzed. Expression of TBK-1, VEGF, RANTES and Il-8 were quantified using qPCR and western blot analysis. Intravital microscopy using the dorsal skinfold chamber model in nude mice addressed total (TIVD) and functional intratumoral vascular density (FIVD), perfusion index, vessel diameter and leukocyte sticking. Transfection of KB-3 cells resulted in significantly increased TBK-1, RANTES and IL-8 expression without affecting cellular growth. Supernatants from TBK-1 overexpressing clones induced HUVEC proliferation. Intravital microscopy identified an increase in leukocyte sticking paralleled by significantly increased TIVD and FIVD as a result of increased VEGF expression. Therefore, TBK-1 represents a novel mediator of tumor angiogenesis and exerts proinflammatory effects via upregulation of inflammatory cytokines. The TBK-1 pathway might be an important cross-link between angiogenesis and inflammation representing a possible target for anti-tumor therapy.
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ISSN:1093-9946
1093-4715
DOI:10.2741/3225