Neutrophil Extracellular Trap-Associated CEACAM1 as a Putative Therapeutic Target to Prevent Metastatic Progression of Colon Carcinoma

中性粒细胞胞外陷阱相关 CEACAM1 作为预防结肠癌转移进展的假定治疗靶点

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作者:Roni F Rayes, Phil Vourtzoumis, Marianne Bou Rjeily, Rashmi Seth, France Bourdeau, Betty Giannias, Julie Berube, Yu-Hwa Huang, Simon Rousseau, Sophie Camilleri-Broet, Richard S Blumberg, Nicole Beauchemin, Sara Najmeh, Jonathan Cools-Lartigue, Jonathan D Spicer, Lorenzo E Ferri

Abstract

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.

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