Melanoma-derived IL-1 converts vascular endothelium to a proinflammatory and procoagulatory phenotype via NF kappa B activation

Strozyk, Elwira A. and Desch, Anna and Poeppelmann, Birgit and Magnolo, Nina and Wegener, Joachim and Huck, Volker and Schneider, Stefan W. (2014) Melanoma-derived IL-1 converts vascular endothelium to a proinflammatory and procoagulatory phenotype via NF kappa B activation. EXPERIMENTAL DERMATOLOGY, 23 (9). pp. 670-676. ISSN 0906-6705, 1600-0625

Full text not available from this repository. (Request a copy)

Abstract

Spreading of melanoma is associated with efficient extravasation of circulating tumor cells from the vascular system into distant target organs. This process is accompanied and supported by proinflammatory and procoagulatory conditions. In this study, we analysed the ability of human melanoma cell lines to activate endothelial cells (ECs) in vitro. Some melanoma cells, that is, MV3, were shown to trigger an prompt calcium-flux-dependent, procoagulatory endothelial response that was accompanied by luminal release of ultra-large von Willebrand factor (ULVWF) fibres that were immobilized to the endothelial surface layer. In contrast to MV3-derived supernatant, prolonged treatment of ECs with WM9-derived supernatant mediated a pronounced activation of nuclear factor kappa B (NFB). NFB activation in ECs was dependent on both IL-1 and IL-1 secreted from melanoma cells. Melanoma-derived IL-1 mediated an upregulation of proinflammatory cytokines IL-6 and IL-8, the intercellular adhesion molecule-1 (ICAM-1), the vascular cell adhesion molecule-1 (VCAM-1) and the procoagulatory tissue factor (TF) in ECs. Our data show that melanoma cells activate ECs either directly and within seconds or by an IL-1-mediated NFB activation. Both pathways of EC activation convert the regular repressive function of ECs on inflammation and coagulation to a proinflammatory and procoagulatory surface that supports tumor progression.

Item Type: Article
Uncontrolled Keywords: VON-WILLEBRAND-FACTOR; CELL-ADHESION MOLECULE-1; METASTATIC MALIGNANT-MELANOMA; FLUID SHEAR-STRESS; P-SELECTIN; LEUKOCYTE EXTRAVASATION; PLASMA ADAMTS13; INFLAMMATION; THERAPY; INTERLEUKIN-1; ADAMTS13; IL-6; melanoma; tissue factor; VWF
Subjects: 500 Science > 540 Chemistry & allied sciences
Divisions: Chemistry and Pharmacy > Institut für Analytische Chemie, Chemo- und Biosensorik > Bioanalytik und Biosensorik (Prof. Joachim Wegener)
Depositing User: Dr. Gernot Deinzer
Date Deposited: 27 Aug 2019 12:55
Last Modified: 27 Aug 2019 12:55
URI: https://pred.uni-regensburg.de/id/eprint/9635

Actions (login required)

View Item View Item