Author:
El Rayes Tina,Catena Raúl,Lee Sharrell,Stawowczyk Marcin,Joshi Natasha,Fischbach Claudia,Powell Charles A.,Dannenberg Andrew J.,Altorki Nasser K.,Gao Dingcheng,Mittal Vivek
Abstract
Inflammation is inextricably associated with primary tumor progression. However, the contribution of inflammation to tumor outgrowth in metastatic organs has remained underexplored. Here, we show that extrinsic inflammation in the lungs leads to the recruitment of bone marrow-derived neutrophils, which degranulate azurophilic granules to release the Ser proteases, elastase and cathepsin G, resulting in the proteolytic destruction of the antitumorigenic factor thrombospondin-1 (Tsp-1). Genetic ablation of these neutrophil proteases protected Tsp-1 from degradation and suppressed lung metastasis. These results provide mechanistic insights into the contribution of inflammatory neutrophils to metastasis and highlight the unique neutrophil protease–Tsp-1 axis as a potential antimetastatic therapeutic target.
Publisher
Proceedings of the National Academy of Sciences
Cited by
160 articles.
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