Insulin-Like Growth Factor I-Triggered Cell Migration and Invasion Are Mediated by Matrix Metalloproteinase-9 1
1999; Oxford University Press; Volume: 140; Issue: 4 Linguagem: Inglês
10.1210/endo.140.4.6623
ISSN1945-7170
AutoresE. Mira, Santos Mañes, Rosa Ana Lacalle, Gabriel Márquez, Carlos Martínez‐A,
Tópico(s)Blood Coagulation and Thrombosis Mechanisms
ResumoMCF-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 αvβ5 integrin, a vitronectin receptor. The levels of αv- andβ 5-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 byα vβ5 integrin.
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