國家衛生研究院 NHRI:Item 3990099045/7856
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    题名: The endothelin-integrin axis is involved in macrophage-induced breast cancer cell chemotactic interactions with endothelial cells
    作者: Chen, CC;Chen, LL;Hsu, YT;Liu, KJ;Fan, CS;Huang, TS
    贡献者: National Institute of Cancer Research
    摘要: Elevated macrophage infiltration in tumor tissues is associated with breast cancer metastasis. Cancer cell migration/invasion towards angiogenic microvasculature is a key step in metastatic spread. We therefore studied how macrophages stimulated breast cancer cell interactions with endothelial cells. Macrophages produced cytokines such as interleukin-8 and tumor necrosis factor-alpha to stimulate endothelin (ET) and ET receptor (ETR) expression in breast cancer cells and human umbilical vascular endothelial cells (HUVECs). ET-1 was induced to a greater extent from HUVECs than breast cancer cells, resulting in a density difference that facilitated cancer cell chemotaxis toward HUVECs. Macrophages also stimulated breast cancer cell adhesion to HUVECs and transendothelial migration, which were repressed by ET-1 antibody or ETR inhibitors. The ET axis induced integrins such as alphaV and beta1 and their counter-ligands such as intercellular adhesion molecule-2 and P-selectin in breast cancer cells and HUVECs, and antibodies against these integrins efficiently suppressed macrophage-stimulated breast cancer cell interactions with HUVECs. ET-1 induced Ets-like kinase-1 (Elk-1), signal transducer and activator of transcription-3 (STAT-3), and nuclear factor-kappaB (NF-kappaB) phosphorylation in breast cancer cells. Use of inhibitors to prevent their phosphorylation, or ectopic overexpression of dominant-negative IkappaBalpha, perturbed ET-1-induced integrin alphaV and integrin beta1 expression. The physical associations of these three transcriptional factors with the gene promoters of the two integrins were furthermore evidenced by chromatin immunoprecipitation assay. Finally, our mouse orthotopic tumor model revealed an ET axis-mediated lung metastasis of macrophage-stimulated breast cancer cells, supporting that the ET axis was involved in macrophage-enhanced breast cancer cell endothelial interactions.
    日期: 2014-04
    關聯: Journal of Biological Chemistry. 2014 Apr;289(14):10029-10044.
    Link to: http://dx.doi.org/10.1074/jbc.M113.528406
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1083-351X&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000333807000051
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84898077405
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