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首页> 外文期刊>The FASEB Journal >Monocytes mediate metastatic breast tumor cell adhesion to endothelium under flow
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Monocytes mediate metastatic breast tumor cell adhesion to endothelium under flow

机译：单核细胞介导转移性乳腺肿瘤细胞对内皮的粘附性

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Endothelial adhesion is necessary for the hematogenous dissemination of tumor cells. However, the metastatic breast tumor cell MDA-MB-231 does not bind to the endothelium under physiological flow conditions, suggesting alternate mechanisms of adhesion. Since monocytes are highly represented in the tumor microenvironment, and also bind to endothelium during inflammation, we hypothesized that the monocytes assist in the arrest of MDA-MB-231 on the endothelium. Using in vitro models of the dynamic shear environment of the vasculature, we show that TNF-α-activated THP1/primary human monocytes and MDA-MB-231 cells form stable aggregates, and that the monocytes in these aggregates mediate the adhesion of otherwise nonadherent MDA-MB-231 cells to inflamed endothelium under flow (55±2.4 vs. 1.7±0.82 at a shear stress of 0.5 dyn/cm2, P<0.01). We also show that the hydrodynamic forces determine the size and orientation of aggregates adhered to the endothelium, and strongly favor the attachment of small aggregates with tumor cells downstream of flow (74–86% doublets at 0.5–2 dyn/cm2, P<0.01). The 5-fold up-regulation of ICAM-1 on TNF-α-activated MDA-MB-231 cells through the Nf-κB pathway was found to be critical in MDA-MB-231–monocyte aggregation and endothelial adhesion. Our results demonstrate that, under inflammatory conditions, monocytes may serve to disseminate tumor cells through circulation, and the tumor–monocyte–endothelial axis may represent a new therapeutic target to reduce cancer metastasis.—Evani, S. J., Prabhu, R. G., Gnanaruban, V., Finol, E. A., Ramasubramanian, A. K. Monocytes mediate metastatic breast tumor cell adhesion to endothelium under flow.
机译：内皮粘附是肿瘤细胞的血液发生筛选所必需的。然而，转移性乳腺肿瘤细胞MDA-MB-231在生理流动条件下不与内皮结合，表明替代的粘合机制。由于单核细胞在肿瘤微环境中高度代表，并且在炎症期间也与内皮结合，我们假设单核细胞有助于在内皮上停止MDA-MB-231。使用脉管系统动态剪切环境的体外模型，我们表明TNF-α-活化的THP1 /原发性人单核细胞和MDA-MB-231细胞形成稳定的聚集体，并且这些聚集体中的单核细胞介导其他否则的粘附性MDA-MB-231细胞在流动下发炎内皮（55±2.4与1.7±0.82，剪切应力为0.5达克/ cm2，P <0.01）。我们还表明，流体动力决定了粘附在内皮上的聚集体的尺寸和取向，并强烈支持将小聚集体与流动下游的肿瘤细胞的附着（0.5-200-200-2000，P <0.01 ）。发现通过NF-κB途径对TNF-α-活化的MDA-MB-231细胞进行ICAM-1的5倍上调在MDA-MB-231-单核细胞聚集和内皮粘附中是至关重要的。我们的结果表明，在炎症条件下，单核细胞可以用于通过循环传播肿瘤细胞，并且肿瘤 - 单核细胞内皮轴可以代表减少癌症转移的新治疗靶标.-Evani，SJ，Prabhu，RG，Gnanaruban，V 。，芬粮，ea，ramasubramanian，Ak单核细胞介导转移性乳腺肿瘤细胞的粘附到流量的内皮。

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