MPO catalytic activity is critical during the early stages of tumor development
Short summary of Rymaszewski, A et al; The Role of Neutrophil Myeloperoxidase in Models of Lung Tumor Development
Lung cancer remains the major cause of cancer-related death in the Western World. Identification of molecular targets of prevention and evaluation of non-toxic agents in pre-clinical animal models of lung cancer is a necessary prerequisite to chemoprevention in humans.
Neutrophils contain numerous substances used to defend against pathogens and to mediate wound healing in tissue. Some of the neutrophil cytoplasmic granule components have been proposed to contribute to tumor proliferation, angiogenesis and metastasis. One of these is myeloperoxidase (MPO), a heme peroxidase enzyme that neutrophils express and secrete, that generates reactive oxygen/nitrogen species (ROS/RNS) as a mechanism for pathogen removal.
The MPO inhibitor N-acetyl lysyltyrosylcysteine amide (KYC) did not affect BHT-induced levels of MPO protein in the BALF. KYC is a reversible inhibitor of MPO and does not irreversibly damage the enzyme as compared to other substrate inhibitors.
Our observations suggest that MPO catalytic activity is critical during the early stages of tumor development. However, during the later stages of tumor progression, MPO expression independent of catalytic activity appears to be required. Our studies advocate for the use of MPO inhibitors in a lung cancer prevention setting.