Rimmaudo Laura Elizabeth, de la Torre Eulalia, Sacerdote de Lustig Eugenia, Sales Maria Elena
Area Investigación, Instituto de Oncología A.H. Roffo, Facultad de Medicina, Universidad de Buenos Aires, Av. San Martin 5481 CP 1417, Buenos Aires, Argentina.
Biochem Biophys Res Commun. 2005 Sep 9;334(4):1359-64. doi: 10.1016/j.bbrc.2005.07.031.
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 M3 receptor subtype. The muscarinic agonist carbachol (CARB) 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 M3 and M1 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.
血管生成是一个从已有的脉管系统发育出新血管的过程，它在肿瘤生长和转移中起着至关重要的作用。在此，我们研究毒蕈碱型乙酰胆碱受体（mAchR）的表达及其在肿瘤细胞增殖和血管生成能力中的作用。用氚标记的毒蕈碱拮抗剂苄基喹宁环酯进行的饱和结合试验表明，源自小鼠乳腺腺癌的LMM3细胞表达单一类型的功能性mAchR。用选择性毒蕈碱拮抗剂进行的竞争结合试验表明M3受体亚型占主导。毒蕈碱激动剂卡巴胆碱（CARB）以浓度依赖的方式刺激LMM3细胞增殖。10(-9)M CARB诱导的最大效应分别被阿托品以及选择性M3和M1拮抗剂对氟六氢硅二苯醇（pf-HHSiD）和哌仑西平完全抑制。此外，pf-HHSiD完全阻断了体内CARB诱导的LMM3肿瘤细胞中的新血管形成和血管内皮生长因子-A。我们可以得出结论，LMM3乳腺肿瘤细胞中表达的mAchR正向调节肿瘤进展所需的增殖和血管生成。
