Myeloperoxidase Alters Lung Cancer Cell Function to Benefit Their Survival
Nejra Cosic-Mujkanovic, Paulina Valadez-Cosmes, Kathrin Maitz, Anna Lueger, Zala N. Mihalic, Marah C. Runtsch, Melanie Kienzl, Michael J. Davies, Christine Y. Chuang, Ákos Heinemann, Rudolf Schicho, Gunther Marsche, Julia Kargl
Abstract
Myeloperoxidase (MPO) is a neutrophil-derived enzyme that has been recently associated with tumour development. However, the mechanisms by which this enzyme exerts its functions remain unclear. In this study, we investigated whether myeloperoxidase can alter the function of A549 human lung cancer cells. We observed that MPO promoted the proliferation of cancer cells and inhibited their apoptosis. Additionally, it increased the phosphorylation of AKT and ERK. MPO was rapidly bound to and internalized by A549 cells, retaining its enzymatic activity. Furthermore, MPO partially translocated into the nucleus and was detected in the chromatin-enriched fraction. Effects of MPO on cancer cell function could be reduced when MPO uptake was blocked with heparin or upon inhibition of the enzymatic activity with the MPO inhibitor 4-aminobenzoic acid hydrazide (4-ABAH). Lastly, we have shown that tumour-bearing mice treated with 4-ABAH had reduced tumour burden when compared to control mice. Our results highlight the role of MPO as a neutrophil-derived enzyme that can alter the function of lung cancer cells.