Lung inflammation promotes metastasis through neutrophil protease-mediated degradation of Tsp-1 Academic Article uri icon

Overview

MeSH Major

  • Lung Neoplasms
  • Neutrophils
  • Peptide Hydrolases
  • Pneumonia
  • Thrombospondin 1

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.

publication date

  • December 29, 2015

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4703007

Digital Object Identifier (DOI)

  • 10.1073/pnas.1507294112

PubMed ID

  • 26668367

Additional Document Info

start page

  • 16000

end page

  • 5

volume

  • 112

number

  • 52