tailieunhanh - Báo cáo khoa học: Inhibition of human MDA-MB-231 breast cancer cell invasion by matrix metalloproteinase 3 involves degradation of plasminogen

Matrix metalloproteinase (MMP)-3 inhibited human MDA-MB-231 breast cancer cell invasion through recon-stituted basement membranein vitro. Inhibition of invasion was dependent upon plasminogen and MMP-3 activation, was impaired by the peptide MMP-3 inhibitor Ac-Arg-Cys-Gly-Val-Pro-Asp-NH2 and was associated with: rapid MMP-3-mediated plasminogen degradation to microplas-minogen and angiostatin-like fragments; | Eur. J. Biochem. 269 4476-4483 2002 FEBS 2002 doi Inhibition of human MDA-MB-231 breast cancer cell invasion by matrix metalloproteinase 3 involves degradation of plasminogen Antonietta R. Farina1 Antonella Tacconelli1 Lucia Cappabianca1 Alberto Gulino2 and Andrew R. Mackay1 1 Section of Molecular Pathology Department of Experimental Medicine University of L Aquila Italy department of Experimental Medicine and Pathology University of Rome La Sapienza Italy Matrix metalloproteinase MMP -3 inhibited human MDA-MB-231 breast cancer cell invasion through reconstituted basement membrane in vitro. Inhibition of invasion was dependent upon plasminogen and MMP-3 activation was impaired by the peptide MMP-3 inhibitor Ac-Arg-Cys-Gly-Val-Pro-Asp-NH2 and was associated with rapid MMP-3-mediated plasminogen degradation to microplasminogen and angiostatin-like fragments the removal of single-chain urokinase plasminogen activator from MDA-MB-231 cell membranes impaired membrane plasminogen association reduced rate of tissue plasminogen activator t-PA and membrane-mediated plasminogen activation and reduced laminin-degrading capacity. Purified human plasminogen lysine binding site-1 kringles 1-3 exhibited a similar capacity to inhibit MDA-MB-231 invasion impair t-PA and cell membrane-mediated plasminogen activation and impair laminin degradation by plasmin. Our data provide evidence that MMP-3 can inhibit breast tumour cell invasion in vitro by a mechanism involving plasminogen degradation to fragments that limit plasminogen activation and the degradation of laminin. This supports the hypothesis that MMP-3 under certain conditions may protect against tumour invasion which would help to explain why MMP-3 expression associated with benign and early stage breast tumours is frequently lost in advanced stage aggressive breast disease. Keywords angiostatin-like invasion laminin matrix metalloproteinase-3 plasminogen. The transition from carcinoma in situ