中性粒细胞胞外陷阱
转移
体内
循环肿瘤细胞
癌症
癌细胞
癌症研究
背景(考古学)
整合素
炎症
医学
免疫学
原发性肿瘤
生物
内科学
受体
古生物学
生物技术
作者
Sara Najmeh,Jonathan Cools‐Lartigue,Roni Rayes,Stephen Gowing,Phil Vourtzoumis,France Bourdeau,Betty Giannias,Julie Bérubé,Simon Rousseau,Lorenzo Ferri,Jonathan Spicer
摘要
Despite advances in cancer treatment, metastasis remains today the main cause of cancer death. Local control through complete surgical resection of the primary tumor continues to be a key principle in cancer treatment. However, surgical interventions themselves lead to adverse oncologic outcomes and are associated with significantly increased rates of metastasis. Neutrophils through release of neutrophil extracellular traps (NETs) in response to infections were shown to be able to capture circulating cancer cells, and in doing so, support the development of metastatic disease. To be able to intervene on this process, understanding the exact molecular nature of these mechanisms is crucial. We therefore hypothesize and demonstrate that β1-integrin is an important factor mediating the interactions between circulating tumor cells and NETs. We show that β1-integrin expression on both cancer cells and NETs is important for the adhesion of circulating tumor cells to NETs both in vitro and in vivo. Using a murine model of intra-abdominal sepsis to mimic the postoperative inflammatory environment, we show that β1-integrin expression is upregulated in the context of inflammation in vivo. Ultimately, we show that this increased early cancer cell adhesion to NETs in vivo and this effect is abrogated when mice are administered DNAse 1. Our data therefore sheds light on the first molecular mechanism by which NETs can trap circulating tumor cells (CTCs), broadening our understanding of this process.
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