Abstract 2823: Exploring the role of neutrophil myeloperoxidase in lung cancer

Abstract

Abstract The aim of this study is to investigate whether myeloperoxidase, a neutrophil-derived molecule in the tumor microenvironment, can influence tumor growth in lung cancer. Lung cancer is the leading cause of cancer related deaths worldwide. Chronic inflammation plays a key role in lung cancer and some studies point out the role of neutrophils as critical mediators of lung carcinogenesis. In this context, some of the neutrophil granule components have been proposed to contribute to tumor development. One of these molecules is myeloperoxidase. Myeloperoxidase is a heme peroxidase enzyme that generates reactive oxygen/nitrogen species and is most abundantly expressed in neutrophils. Upon neutrophil activation, during acute inflammation or in the tumor microenvironment, MPO is secreted into the extracellular milieu during degranulation and utilizes H2O2 to hypochlorous acid that reacts with surrounding proteins and cell surface molecules and thereby can alter signaling pathways and cell functions. So far, we have found some evidence on myeloperoxidase acting in favor of tumor development. In vivo, LSL-K-ras/MPO-/- mice revealed prolonged survival and reduced tumor burden when compared to LSL-K-ras/MPO+/+ mice. Consistently, in a heterotopic syngeneic tumor mouse model, MPO knockout mice (C57/B6-J/MPO-/-) displayed smaller tumors in comparison to the WT littermates. In vitro, myeloperoxidase is able to bind, internalize and preserve its enzymatic activity in human lung adenocarcinoma A549 cells. Furthermore, A549 cells showed increased proliferation and reduced apoptosis after MPO treatment as well as an enhanced phosphorylation of Akt and Erk proteins. According to our current results, myeloperoxidase may play a role in the development of lung cancer by regulating cancer cell function. Moreover, this project sheds light on the role of neutrophil-derived molecules as key players in the context of tumor growth. Citation Format: Paulina Valadez-Cosmes, Nejra Cosic, Melanie Kienzl, Kathrin Maitz, Sofia Raftopoulou, A. McGarry Houghton, Akos Heinemann, Michael J. Davies, Julia Kargl. Exploring the role of neutrophil myeloperoxidase in lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2823.