Role of imbalance between neutrophil elastase and alpha 1-antitrypsin in cancer development and progression

Neutrophil elastase and alpha 1-antitrypsin are a pair of protease and protease inhibitor counterparts. The imbalance between the two counterparts is generally thought to cause tissue damage, which could create a favourable tissue environment for carcinogens and tumour progression. Laboratory research and clinical findings have indicated that a deficiency in alpha1-antitrypsin is associated with increased risk of liver cancer, bladder cancer, gall bladder cancer, malignant lymphoma, and lung cancer. Conversely, raised concentrations of neutrophil elastase might promote the development, invasion, and metastasis of many cancers. Several mechanisms of carcinogenesis have been postulated. Excess neutrophil elastase might facilitate cancer development by causing tissue damage and air trapping, which foster longer carcinogen exposure, might promote cancer progression by degrading the intercellular matrix barrier, and might directly lead to cancer development through the tumour-necrosis-factor signalling pathway.