前期的临床研究和小鼠模型的工作表明，血小板和微小血块可能作为协助因素，在预转移癌生物学场中招募免疫细胞，从而通过血管壁使癌细胞成功越过血管内膜。在此，我们通过对透明斑马鱼幼体进行活体成像研究，调查了血小板、内皮细胞、炎症细胞和移植的人类和斑马鱼癌细胞之间的相互作用，并展示了凝血（以及凝块消化）作为病灶和癌细胞越过内皮的触发因子的机制。通过对每个细胞谱系的荧光标记，揭示了它们在这一过程中的动态行为和潜在作用，并通过使贡献因子的基因和药物进行敲除来测试其功能。纤维蛋白的形态制品敲除和华法林抑制凝血的治疗均使癌细胞的越过内皮降低。炎症表型似乎是基本的，我们展示了强制患有促炎性的TNFa+ve表型对癌细胞的越过内皮具有抑制作用。© 2023. 由生物学家公司出版。

Previous clinical studies and work in mouse models have indicated that platelets and microclots may function as enablers in the recruitment of immune cells to the pre-metastatic cancer niche leading to efficacious extravasation of cancer cells through the vessel wall. Here we investigate the interaction between platelets, endothelial cells, inflammatory cells and engrafted human and zebrafish cancer cells by live imaging studies in translucent zebrafish larvae, and show how clotting (and clot resolution) act as foci and as triggers for extravasation. Fluorescent tagging of each lineage reveals their dynamic behaviour and potential roles in these events, and we test function by genetic and drug knockdown of the contributing players. Morpholino knockdown of fibrin, and warfarin treatment to inhibit clotting, both abrogate extravasation of cancer cells. Inflammatory phenotype appears fundamental, and we show that forcing a pro-inflammatory, TNFa+ve phenotype is inhibitory to extravasation of cancer cells.© 2023. Published by The Company of Biologists Ltd.