Insulin-like growth factor I-triggered cell migration and invasion are mediated by matrix metalloproteinase-9.
MCF-7 cells migrate through vitronectin-coated filters in response to insulin-like growth factor I (IGF-I); migration is inhibited by the matrix metalloproteinase (MMP) inhibitor BB-94, but not by the serine proteinase inhibitor aprotinin. MMP-9 was identified in the conditioned medium of MCF-7 cells; in addition, fluorescence-activated cell sorting analysis revealed its presence on the cell surface, where MMP-9 activity was also found using a specific fluorogenic peptide. Furthermore, the messenger RNA encoding MMP-9 was detected in MCF-7 cells by PCR. The IGF-I concentration leading to maximal MCF-7 invasion produces an increase in cell surface proteolytic activity after short incubation periods. At 18 h, however, preincubation of MCF-7 cells with IGF-I produces at 18 h a dose-dependent decrease in cell-associated MMP-9 activity and an increase in soluble MMP-9. MCF-7 invasion is dependent on the alpha(v)beta5 integrin, a vitronectin receptor. The levels of alpha(v)- and beta5-subunits expressed in MCF-7 cells depend on the IGF-I concentration, which triggers an increase in both of these subunits. Based on these results, we suggest that IGF-I-induced MCF-7 cell migration is mediated by the MMP-9 activity on the cell surface and by alpha(v)beta5 integrin.
Mira
E
E
Department of Immunology and Oncology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Spain. emira@cnb.uam.es
Mañes
S
S
Lacalle
R A
RA
Márquez
G
G
Martínez-A
C
C
D001943:Breast Neoplasms / Q000201:enzymology / Q000473:pathology*; D002462:Cell Membrane / Q000201:enzymology; D002465:Cell Movement; D017364:Collagenases / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D017077:Culture Media, Conditioned; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D016023:Integrins / Q000378:metabolism; D020780:Matrix Metalloproteinase 9; D009361:Neoplasm Invasiveness; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D011480:Protease Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D019030:Receptors, Vitronectin; D013876:Thiophenes / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D017077:Culture Media, Conditioned; D016023:Integrins; D011480:Protease Inhibitors; D012333:RNA, Messenger; D019030:Receptors, Vitronectin; D013876:Thiophenes; C064660:integrin alphaVbeta5; D010649:Phenylalanine; D007334:Insulin-Like Growth Factor I; C080985:batimastat; D017364:Collagenases; D020780:Matrix Metalloproteinase 9