Selectin-mediated activation of endothelial cells induces expression of CCL5 and promotes metastasis through recruitment of monocytes
Selectin-mediated activation of endothelial cells induces expression of CCL5 and promotes metastasis through recruitment of monocytes
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DOI：
10.1182/blood-2008-10-186585
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发表时间：
2009-11-12
期刊：
影响因子：
20.3
通讯作者：
Borsig, Lubor
中科院分区：
文献类型：
--
作者：
Laeubli, Heinz;Spanaus, Katharina-Susanne;Borsig, Lubor
肿瘤细胞与局部血管内微环境中的白细胞、血小板和内皮细胞的相互作用促进了血行转移。在这里，我们表明，微血管内皮细胞的激活导致单核细胞的招聘转移性肿瘤细胞，并促进转移性微环境的建立。这种炎症样内皮反应仅在微血管内皮细胞中观察到。微血管内皮细胞与肿瘤细胞在白细胞和血小板的存在下共培养的微阵列分析揭示了一个特定的基因表达谱。选择素介导的肿瘤细胞与血小板和白细胞的相互作用激活内皮细胞并诱导C-C趋化因子配体5（CCL 5）的产生。通过CCL 5受体拮抗剂在转移的早期阶段抑制CCL 5依赖性单核细胞募集强烈降低肿瘤细胞存活和减弱转移。总的来说，这些发现表明，CCL 5的内皮表达有助于形成一个允许的转移微环境。（血。2009; 114：4583-4591）
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 plateletsandleukocytes 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. ( Blood. 2009; 114: 4583-4591)