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Blood, 12 November 2009, Vol. 114, No. 20, pp. 4583-4591. Prepublished online as a Blood First Edition Paper on September 24, 2009; DOI 10.1182/blood-2008-10-186585. This Article Full Text Full Text (PDF) Supplemental Table and Figures Additional Supplemental Figures All Versions of this Article: blood-2008-10-186585v1 114/20/4583    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Google Scholar Articles by Läubli, H. Articles by Borsig, L. PubMed PubMed Citation Articles by Läubli, H. Articles by Borsig, L. Related Collections Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  VASCULAR BIOLOGY Selectin-mediated activation of endothelial cells induces expression of CCL5 and promotes metastasis through recruitment of monocytes Heinz Läubli1,2, Katharina-Susanne Spanaus3, and Lubor Borsig1,2 1 Institute of Physiology, University of Zürich, Zürich; 2 Zürich Center for Integrative Human Physiology, Zürich; and 3 Institute of Clinical Chemistry, University Hospital Zürich, Zürich, Switzerland Hematogenous metastasis is promoted by interactions of tumor cells with leukocytes, platelets, and the endothelium in the local intravascular microenvironment. Here we show that the activation of the microvascular endothelium results in recruitment of monocytes to metastatic tumor cells and promotes the establishment of the metastatic microenvironment. This inflammatory-like endothelial response was observed in microvascular endothelial cells only. Microarray analysis of microvascular endothelial cells cocultured with tumor cells in the presence of leukocytes and platelets revealed a specific gene expression profile. Selectin-mediated interactions of tumor cells with platelets and leukocytes activated endothelial cells and induced production of C-C chemokine ligand 5 (CCL5). Inhibition of CCL5-dependent monocyte recruitment during the early phase of metastasis by a CCL5 receptor antagonist strongly reduced tumor cell survival and attenuated metastasis. Collectively, these findings demonstrate that the endothelial expression of CCL5 contributes to the formation of a permissive metastatic microenvironment. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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