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Platelets guide the formation of early metastatic niches

机译:血小板指导早期转移性龛的形成

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摘要

During metastasis, host cells are recruited to disseminated tumor cells to form specialized microenvironments (“niches”) that promote metastatic progression, but the mechanisms guiding the assembly of these niches are largely unknown. Tumor cells may autonomously recruit host cells or, alternatively, host cell-to-host cell interactions may guide the formation of these prometastatic microenvironments. Here, we show that platelet-derived rather than tumor cell-derived signals are required for the rapid recruitment of granulocytes to tumor cells to form “early metastatic niches.” Granulocyte recruitment relies on the secretion of CXCL5 and CXCL7 chemokines by platelets upon contact with tumor cells. Blockade of the CXCL5/7 receptor CXCR2, or transient depletion of either platelets or granulocytes prevents the formation of early metastatic niches and significantly reduces metastatic seeding and progression. Thus, platelets recruit granulocytes and guide the formation of early metastatic niches, which are crucial for metastasis.
机译:在转移过程中,宿主细胞被募集到已扩散的肿瘤细胞中,以形成促进转移进程的专门的微环境(“生态位”),但是指导这些生态位装配的机制在很大程度上尚不清楚。肿瘤细胞可以自主募集宿主细胞,或者宿主细胞与宿主细胞的相互作用可以指导这些前转移微环境的形成。在这里,我们显示了血小板来源而不是肿瘤细胞来源的信号是粒细胞快速募集到肿瘤细胞以形成“早期转移的利基”所必需的。粒细胞募集依赖于与肿瘤细胞接触后血小板产生的CXCL5和CXCL7趋化因子的分泌。 CXCL5 / 7受体CXCR2的阻滞或血小板或粒细胞的短暂耗竭阻止了早期转移性壁ni的形成,并显着降低了转移性播种和进展。因此,血小板募集粒细胞并指导早期转移性ni的形成,这对于转移至关重要。

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