Inhibition of human MDAâMBâ231 breast cancer cell invasion by matrix metalloproteinase 3 involves degradation of plasminogen
2002
Farina, Antonietta R. | Tacconelli, Antonella | Cappabianca, Lucia | Gulino, Alberto | Mackay, Andrew R
Matrix metalloproteinase (MMP)â3 inhibited human MDAâMBâ231 breast cancer cell invasion through reconstituted basement membrane in vitro. Inhibition of invasion was dependent upon plasminogen and MMPâ3 activation, was impaired by the peptide MMPâ3 inhibitor AcâArgâCysâGlyâValâProâAspâNH2 and was associated with: rapid MMPâ3âmediated plasminogen degradation to microplasminogen and angiostatinâlike fragments; the removal of singleâchain urokinase plasminogen activator from MDAâMBâ231 cell membranes; impaired membrane plasminogen association; reduced rate of tissue plasminogen activator (tâPA) and membraneâmediated plasminogen activation; and reduced lamininâdegrading capacity. Purified human plasminogen lysine binding siteâ1 (kringles 1–3) exhibited a similar capacity to inhibit MDAâMBâ231 invasion, impair tâPA and cell membraneâmediated plasminogen activation and impair laminin degradation by plasmin. Our data provide evidence that MMPâ3 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 MMPâ3, under certain conditions, may protect against tumour invasion, which would help to explain why MMPâ3 expression, associated with benign and early stage breast tumours, is frequently lost in advanced stage, aggressive, breast disease.
Show more [+] Less [-]AGROVOC Keywords
Bibliographic information
This bibliographic record has been provided by National Agricultural Library