中性粒细胞胞外陷阱
癌症研究
化疗
转移
分泌物
肿瘤微环境
癌细胞
癌症
转化生长因子
细胞外基质
生物
基质金属蛋白酶
免疫学
炎症
医学
细胞生物学
内科学
内分泌学
肿瘤细胞
作者
Alexandra Mousset,Enora Lecorgne,Isabelle Bourget,Pascal Lopez,Kitti Jenovai,Julien Cherfils‐Vicini,Chloé Dominici,Géraldine Rios,Cédric Girard-Riboulleau,Bodu Liu,David L. Spector,Sidse Ehmsen,Shufang Renault,Caroline Hego,Fatima Mechta‐Grigoriou,François‐Clément Bidard,Mikkel G. Terp,Mikala Egeblad,Cédric Gaggioli,Jean Albrengues
出处
期刊:Cancer Cell
[Elsevier]
日期:2023-04-01
卷期号:41 (4): 757-775.e10
被引量:65
标识
DOI:10.1016/j.ccell.2023.03.008
摘要
Summary
Metastasis is the major cause of cancer death, and the development of therapy resistance is common. The tumor microenvironment can confer chemotherapy resistance (chemoresistance), but little is known about how specific host cells influence therapy outcome. We show that chemotherapy induces neutrophil recruitment and neutrophil extracellular trap (NET) formation, which reduces therapy response in mouse models of breast cancer lung metastasis. We reveal that chemotherapy-treated cancer cells secrete IL-1β, which in turn triggers NET formation. Two NET-associated proteins are required to induce chemoresistance: integrin-αvβ1, which traps latent TGF-β, and matrix metalloproteinase 9, which cleaves and activates the trapped latent TGF-β. TGF-β activation causes cancer cells to undergo epithelial-to-mesenchymal transition and correlates with chemoresistance. Our work demonstrates that NETs regulate the activities of neighboring cells by trapping and activating cytokines and suggests that chemoresistance in the metastatic setting can be reduced or prevented by targeting the IL-1β-NET-TGF-β axis.
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