Muscarinic receptors are involved in LMM3 tumor cells proliferation and angiogenesis.
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.
Rimmaudo
Laura Elizabeth
LE
Area Investigación, Instituto de Oncología A.H. Roffo, Facultad de Medicina, Universidad de Buenos Aires, Av. San Martin 5481 CP 1417, Buenos Aires, Argentina.
de la Torre
Eulalia
E
Sacerdote de Lustig
Eugenia
E
Sales
Maria Elena
ME
D000230:Adenocarcinoma / Q000098:blood supply* / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D008325:Mammary Neoplasms, Experimental / Q000098:blood supply* / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology*; D011976:Receptors, Muscarinic / Q000378:metabolism*
D011976:Receptors, Muscarinic