Synthesis of acetylcholine by lung cancer
Synthesis of acetylcholine by lung cancer
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DOI：
10.1016/s0024-3205(03)00078-x
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发表时间：
2003-03-28
期刊：
影响因子：
6.1
通讯作者：
Spindel, ER
中科院分区：
文献类型：
--
作者：
Song, P;Sekhon, HS;Spindel, ER
自分泌生长因子在促进肺癌生长中的作用已得到证实。尼古丁是一种乙酰胆碱受体的激动剂，能刺激肺癌的生长。这提示如果肺癌合成乙酰胆碱（ACh），那么ACh可能是肺癌的自分泌生长因子。对正常肺的分析表明，肺癌起源细胞表达非神经元乙酰胆碱储存和合成所必需的蛋白质。鳞状细胞肺癌、小细胞肺癌和腺癌mRNA表达分析。胆碱乙酰转移酶（ChAT）和烟碱受体的合成。对一系列SCLC和腺癌的回顾性免疫组化分析显示，超过50%的筛查肺癌表达ChAT和烟碱受体。为了研究内源性乙酰胆碱合成对SCLC细胞株生长的影响。通过HPLC分离和酶偶联电化学检测，发现SCLC细胞系表达ChAT mRNA，并向培养基中分泌ACh。SCLC细胞系NCI-H82乙酰胆碱合成水平最高。说明内源性合成的乙酰胆碱与其受体相互作用刺激细胞生长，添加毒蕈碱和烟碱拮抗剂可减缓H82细胞的增殖。这些发现表明，肺癌细胞系可以合成和分泌乙酰胆碱作为一种自分泌生长因子。肺癌中胆碱能自分泌环的存在为了解香烟烟雾中尼古丁对肺癌生长的影响提供了基础，并为探索潜在的肺癌治疗方法提供了新的途径。(C) 2003爱思唯尔科学有限公司版权所有。
The role of autocrine growth factors in the stimulation of lung cancer growth is well established. Nicotine is an agonist for acetylcholine receptors and stimulates lung cancer growth. This suggests that if lung cancers synthesize acetylcholine (ACh), then ACh may be an autocrine growth factor for lung cancer. Analysis of normal lung demonstrated that the cells of origin of lung cancers express the proteins necessary for non-neuronal ACh storage and synthesis. Analysis of mRNA from squamous cell lung carcinoma, small cell lung carcinoma (SCLC) and adenocarcinoma. showed synthesis of choline acetyltransferase (ChAT) and nicotinic receptors. Immunohistochemical analysis of a retrospective series of SCLC and adenocarcinomas showed that more than 50% of the lung cancers screened expressed ChAT and nicotinic receptors. To study the effect of endogenous ACh synthesis on growth, SCLC cell lines were studied. SCLC cell lines were found to express ChAT mRNA and to secrete ACh into the medium as measured by HPLC separation and enzymatically-coupled electrochemical detection. The SCLC cell line NCI-H82 synthesized highest levels of ACh. Showing that the endogenously synthesized ACh interacted with its receptors to stimulate cell growth, addition of muscarinic and nicotinic antagonists slowed H82 cell proliferation. These findings demonstrate that lung cancer cell lines synthesize and secrete ACh to act as an autocrine growth factor. The existence of a cholinergic autocrine loop in lung cancer provides a basis for understanding the effects of nicotine in cigarette smoke on lung cancer growth and provides a new pathway to investigate for potential therapeutic approaches to lung cancer. (C) 2003 Elsevier Science Inc. All rights reserved.