Bowen Zhang1, Chenzhou Wu1, Wen Chen1, Ling Qiu1, Shensui Li1, Tao Wang1, Huixu Xie1, Yi Li1, Chunjie Li1, Longjiang Li2. 1. State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Head and Neck Oncology Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China. 2. State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Head and Neck Oncology Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China. Electronic address: muzili63@163.com.
Abstract
OBJECTIVE: Chronic stress hormone norepinephrine (NE) has been previously reported to play a role in the development of cancer, but the correlation between NE and oral squamous cell carcinoma (OSCC) progression is not well understood. METHOD: To address this, the expression of adrenergic receptors (ARs) in human OSCC cell lines and clinic OSCC samples was detected, and the role of NEin vivo and in vitro was further investigated. RESULTS: It was found that β2-AR was the main AR of NE in OSCC. Stimulation of OSCC cells with NE significantly increased the OSCC proliferation and invasion, which was, however, blocked by β2-AR inhibitor. NE could induce the phosphorylation of extracellular regulated protein kinases (ERK) and cAMP-response element binding protein (CREB). Inhibition of ERK and CREB pathway abrogated NE-induced OSCC invasion and proliferation. NE could enhance cancer stem cells (CSCs)-like phenotype and up-regulate the expression of stemness marker. In tumor-bearing nude mice, it was found that consecutive administration of NE significantly promoted the tumor growth, while daily injection of β2-AR inhibitor blocked this phenomenon. CONCLUSIONS: Those findings indicated a critical role of the chronic stress hormone NE in OSCC progression. Inhibition of β2-AR may serve as a potential therapeutic strategy for protecting OSCC patients from chronic stress related deleterious effect.
OBJECTIVE: Chronic stress hormone norepinephrine (NE) has been previously reported to play a role in the development of cancer, but the correlation between NE and oral squamous cell carcinoma (OSCC) progression is not well understood. METHOD: To address this, the expression of adrenergic receptors (ARs) in humanOSCC cell lines and clinic OSCC samples was detected, and the role of NEin vivo and in vitro was further investigated. RESULTS: It was found that β2-AR was the main AR of NE in OSCC. Stimulation of OSCC cells with NE significantly increased the OSCC proliferation and invasion, which was, however, blocked by β2-AR inhibitor. NE could induce the phosphorylation of extracellular regulated protein kinases (ERK) and cAMP-response element binding protein (CREB). Inhibition of ERK and CREB pathway abrogated NE-induced OSCC invasion and proliferation. NE could enhance cancer stem cells (CSCs)-like phenotype and up-regulate the expression of stemness marker. In tumor-bearing nude mice, it was found that consecutive administration of NE significantly promoted the tumor growth, while daily injection of β2-AR inhibitor blocked this phenomenon. CONCLUSIONS: Those findings indicated a critical role of the chronic stress hormone NE in OSCC progression. Inhibition of β2-AR may serve as a potential therapeutic strategy for protecting OSCCpatients from chronic stress related deleterious effect.
Authors: Simon Grelet; Cécile Fréreux; Clémence Obellianne; Ken Noguchi; Breege V Howley; Annamarie C Dalton; Philip H Howe Journal: Life Sci Alliance Date: 2021-11-22
Authors: Jessica Hedderich; Karima El Bagdadi; Peter Angele; Susanne Grässel; Andrea Meurer; Rainer H Straub; Frank Zaucke; Zsuzsa Jenei-Lanzl Journal: Int J Mol Sci Date: 2020-05-30 Impact factor: 5.923