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Melanoma‐derived IL ‐1 converts vascular endothelium to a proinflammatory and procoagulatory phenotype via NF κ B activation
Author(s) -
Strozyk Elwira A.,
Desch Anna,
Poeppelmann Birgit,
Magnolo Nina,
Wegener Joachim,
Huck Volker,
Schneider Stefan W.
Publication year - 2014
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.12505
Subject(s) - proinflammatory cytokine , melanoma , chemistry , endothelial activation , microbiology and biotechnology , inflammation , endothelium , downregulation and upregulation , endothelial stem cell , cell adhesion molecule , extravasation , tumor necrosis factor alpha , tissue factor , cancer research , immunology , biology , in vitro , coagulation , endocrinology , biochemistry , medicine , gene
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 ( EC s) in vitro . Some melanoma cells, that is, MV 3, 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 MV 3‐derived supernatant, prolonged treatment of EC s with WM 9‐derived supernatant mediated a pronounced activation of nuclear factor kappa B ( NF κ B). NF κ B activation in EC s was dependent on both IL ‐1 α and IL ‐1 β 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 EC s. Our data show that melanoma cells activate EC s either directly and within seconds or by an IL ‐1‐mediated NF κ B activation. Both pathways of EC activation convert the regular repressive function of EC s on inflammation and coagulation to a proinflammatory and procoagulatory surface that supports tumor progression.