Open AccessADRB3 expression in tumor cells is a poor prognostic factor and promotes proliferation in non-small cell lung carcinoma
Author(s) -
Zheng Meng,
ZhiLing Zhou,
Tian Xia,
Dingzhang Xiao,
Xinghua Hou,
Zhi Xie,
Haidan Liang,
Shu Lin
Publication year - 2020
Publication title -
cancer immunology, immunotherapy/cancer immunology and immunotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.389
H-Index - 115
eISSN - 1432-0851
pISSN - 0340-7004
DOI - 10.1007/s00262-020-02627-3
Subject(s) - lung cancer , cancer research , biology , downregulation and upregulation , inflammation , cell growth , carcinoma , cancer , tumor progression , cancer stem cell , immunology , stem cell , medicine , pathology , microbiology and biotechnology , gene , genetics , biochemistry
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.