At the same time, tumor-secreted cathepsin C also up-regulated neutrophils reactive oxygen species (ROS) levels through PR3-IL-1β-P38/mitogen-activated protein kinase (MAPK), inducing the formation of NETs to degrade the anti-tumor factor thrombospondin-1 (Tsp-1) in lungs metastasis microenvironment. The gene discussed is THBS1; the disease is neoplasm.