ADRB3 expression in tumor cells is a poor prognostic factor and promotes proliferation in non-small cell lung carcinoma
- PDF / 1,935,782 Bytes
- 11 Pages / 595.276 x 790.866 pts Page_size
- 73 Downloads / 170 Views
ORIGINAL ARTICLE
ADRB3 expression in tumor cells is a poor prognostic factor and promotes proliferation in non‑small cell lung carcinoma Meng Zheng1 · Zhiling Zhou2 · Xiangting Tian1 · Dingzhang Xiao1 · Xinghua Hou1 · Zhi Xie1 · Haidan Liang1 · Shuguang Lin1 Received: 27 December 2019 / Accepted: 28 May 2020 © The Author(s) 2020
Abstract The cross-talk between cancer cells and monocyte-derived alveolar macrophages (Mo-AMs) promotes non-small cell lung carcinoma (NSCLC) progression. In this study, we report that both cancer cells and Mo-AMs robustly express beta 3-adrenergic receptor (ADRB3) in NSCLC. ADRB3 supports lung cancer cells proliferation and promotes chronic inflammation. Genetic and pharmacologic inhibition of ADRB3 reverses tumor growth and inflammation in mouse. Furthermore, we demonstrate that M5D1, a novel anti-ADRB3 monoclonal antibody, inhibits human lung cancer cells proliferation and inflammation via affecting the intracellular mTOR pathway and activating p53. In NSCLC patients, we confirmed that upregulation of ADRB3 expression correlates with tumor progression and poor prognosis. Altogether, these results shed light on the role of ADRB3 in NSCLC and suggest that M5D1 could become powerful antitumor weapons. Keywords ADRB3 · Macrophage · Lung cancer · Inflammation · Monoclonal antibody · mTOR Abbreviations AC Adenocarcinoma ADRB3 Beta 3-adrenergic receptor AMs Alveolar macrophages EMSA Electrophoretic mobility shift assay FBS Fetal bovine serum ICI Inflammatory cell infiltration IHC Immunohistochemistry IL-6 Interleukin-6 Mo-AMs Monocyte-derived alveolar macrophages MPO Myeloperoxidase NLR Neutrophil–lymphocyte ratio NSCLC Non-small cell lung carcinoma Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00262-020-02627-3) contains supplementary material, which is available to authorized users. * Meng Zheng [email protected] * Shuguang Lin [email protected] 1
Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China
Zhuhai People’s Hospital, Zhuhai Hospital Affiliated with Jinan University, Zhuhai, China
2
PBMCs Peripheral blood mononuclear cells PD-1 Programmed cell death 1 PI Propidium iodide SCC Squamous cell carcinoma SNS Sympathetic nervous system siRNA Small interfering RNA TMA Tissue microarray TC Tumor cells
Introduction The number of deaths from lung cancer is higher than the number of deaths caused by breast, colon and prostate cancers [1]. NSCLC constitutes over 80% of all lung cancer cases [2]. This group includes mainly squamous cell carcinoma (SCC) and adenocarcinoma (AC) [3]. The latest method of immunotherapy uses monoclonal antibodies directed against the immune-checkpoint molecules such as programmed cell death 1 (PD-1) or its ligand (PD-L1) [4, 5]. Cancer progression is affected significantly by immune system dysfunctions, particularly those that involve generalized immunosuppression and the activation of proinflammatory cell pathways [6]. Cancer-related inflammati
Data Loading...
