Muscarinic receptors are involved in LMM3 tumor cells proliferation and angiogenesis
Muscarinic receptors are involved in LMM3 tumor cells proliferation and angiogenesis
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DOI：
10.1016/j.bbrc.2005.07.031
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发表时间：
2005-09-09
影响因子：
3.1
通讯作者：
Sales, ME
中科院分区：
文献类型：
--
作者：
Rimmaudo, LE;de la Torre, E;Sales, ME
血管生成是从已有的血管系统发育出新血管的过程，在肿瘤的生长和转移中起着重要作用。在这里，我们调查的毒蕈碱乙酰胆碱受体（mAchR）的表达和他们参与肿瘤细胞增殖和血管生成能力。用氚化毒蕈碱拮抗剂奎宁环二苯乙酸饱和结合试验表明，来自小鼠乳腺癌的LMM 3细胞表达一类功能性mAchR。与选择性毒蕈碱拮抗剂的竞争结合试验表明，M-3受体亚型的优势。毒蕈碱激动剂卡巴胆碱（GARB）以浓度依赖性方式刺激LMM 3细胞增殖。10（-9）M CARB诱导的最大效应分别被阿托品和选择性M-3和M-1拮抗剂对氟六氢硅地芬尼多（pf-HHSiD）和哌仑西平完全减弱。此外，pf-HHSiD完全阻断LMM 3肿瘤细胞中体内CARB诱导的新生血管形成和血管内皮生长因子-A。我们可以得出结论，在LMM 3乳腺肿瘤细胞中表达的mAchR正调节肿瘤进展所需的增殖和血管生成。(c)2005年爱思唯尔公司All rights reserved.
Angiogenesis is a process of new blood vessel development from pre-existing vasculature and it plays an essential role in tumor growth and metastases. Here, we investigate the expression of muscarinic acetylcholine receptors (mAchR) and their participation in tumor cell proliferation and angiogenesis ability. Saturation binding assays with the tritiated muscarinic antagonist quinuclidinyl benzilate indicate that LMM3 cells derived from a murine mammary adenocarcinoma express a single class of functional mAchR. Competition binding assays with selective muscarinic antagonists indicate a predominance of M-3 receptor subtype. The muscarinic agonist carbachol (GARB) stimulates LMM3 cell proliferation in a concentration dependent manner. The maximal effect induced by 10(-9) M CARB was totally blunted by atropine and by the selective M-3 and M-1 antagonists, para-fluoro hexahydro sila-difenidol (pf-HHSiD) and pirenzepine, respectively. In addition, pf-HHSiD completely blocked in vivo CARB-induced neovascular formation and vascular endothelial growth factor-A in LMM3 tumor cells. We,can conclude that mAchR expressed in LMM3 mammary tumor cells positively regulate proliferation and angiogenesis required for tumor progression. (c) 2005 Elsevier Inc. All rights reserved.