Related Experiment Video
Updated: Jul 18, 2025
The Establishment of a Lung Colonization Assay for Circulating Tumor Cell Visualization in Lung Tissues
Published on: June 16, 2018
Myeloperoxidase Alters Lung Cancer Cell Function to Benefit Their Survival
Nejra Cosic-Mujkanovic1, Paulina Valadez-Cosmes1, Kathrin Maitz1
1Division of Pharmacology, Otto Loewi Research Center, Medical University of Graz, 8010 Graz, Austria.
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.
Insights
Myeloperoxidase (MPO) promotes lung cancer cell growth and survival by increasing proliferation and inhibiting apoptosis. Inhibiting MPO activity with 4-aminobenzoic acid hydrazide (4-ABAH) reduced tumour burden in mice.
Area of Science:
- Biochemistry
- Cell Biology
- Oncology
Background:
- Myeloperoxidase (MPO), an enzyme from neutrophils, is linked to tumor development.
- The precise mechanisms of MPO's role in cancer progression are not fully understood.
Purpose of the Study:
- To investigate the functional impact of MPO on A549 human lung cancer cells.
- To explore the mechanisms underlying MPO's effects on cancer cell behavior and potential therapeutic targets.
Main Methods:
- Assessed MPO's effects on A549 cell proliferation, apoptosis, and signaling pathways (AKT, ERK).
- Investigated MPO binding, internalization, and subcellular localization (including nuclear translocation).
- Utilized heparin to block MPO uptake and 4-aminobenzoic acid hydrazide (4-ABAH) to inhibit MPO activity in vitro and in vivo.
Main Results:
- MPO enhanced A549 cell proliferation and suppressed apoptosis, increasing AKT and ERK phosphorylation.
- MPO was internalized by A549 cells, retained activity, and translocated to the nucleus.
- Blocking MPO uptake or inhibiting its enzymatic activity with 4-ABAH counteracted MPO's pro-cancer effects.
- Treatment with 4-ABAH significantly reduced tumor burden in mice.
Conclusions:
- Myeloperoxidase significantly influences lung cancer cell function, promoting proliferation and survival.
- MPO's enzymatic activity and cellular uptake are critical for its oncogenic effects.
- Inhibiting MPO represents a potential therapeutic strategy for reducing lung cancer progression.
