Cancer Research Program and the LD MacLean Surgical Research Laboratories, Department of Surgery, Research Institute of the McGill University Health Center, Montreal, Quebec H4A 3J1, Canada.
Meakins-Christie Laboratories, Department of Medicine, McGill University and the McGill University Health Center, Montreal, Quebec H4A 3J1, Canada.
J Immunol. 2020 Apr 15;204(8):2285-2294. doi: 10.4049/jimmunol.1900240. Epub 2020 Mar 13.
Neutrophils promote tumor growth and metastasis at multiple stages of cancer progression. One mechanism through which this occurs is via release of neutrophil extracellular traps (NETs). We have previously shown that NETs trap tumor cells in both the liver and the lung, increasing their adhesion and metastasis following postoperative complications. Multiple studies have since shown that NETs play a role in tumor progression and metastasis. NETs are composed of nuclear DNA-derived web-like structures decorated with neutrophil-derived proteins. However, it is unknown which, if any, of these NET-affiliated proteins is responsible for inducing the metastatic phenotype. In this study, we identify the NET-associated carcinoembryonic Ag cell adhesion molecule 1 (CEACAM1) as an essential element for this interaction. Indeed, blocking CEACAM1 on NETs, or knocking it out in a murine model, leads to a significant decrease in colon carcinoma cell adhesion, migration and metastasis. Thus, this work identifies NET-associated CEACAM1 as a putative therapeutic target to prevent the metastatic progression of colon carcinoma.
中性粒细胞在癌症进展的多个阶段促进肿瘤生长和转移。其中一种发生机制是通过释放中性粒细胞胞外诱捕网(NETs)。我们之前已经表明,NETs 在肝脏和肺部捕获肿瘤细胞,增加了它们在术后并发症后的粘附和转移。此后,多项研究表明 NETs 在肿瘤进展和转移中发挥作用。NETs 由核 DNA 衍生的网状结构组成,这些结构被中性粒细胞衍生的蛋白质所装饰。然而,目前尚不清楚这些与 NET 相关的蛋白质中,有哪些是负责诱导转移表型的。在这项研究中,我们确定了与 NET 相关的癌胚抗原细胞粘附分子 1(CEACAM1)是这种相互作用的关键因素。事实上,阻断 NET 上的 CEACAM1 或在小鼠模型中敲除它,可导致结肠癌细胞的粘附、迁移和转移显著减少。因此,这项工作确定了与 NET 相关的 CEACAM1 是预防结肠腺癌转移进展的一个潜在治疗靶点。