Insulin-like Growth Factor I-triggered Cell Migration and Invasion Are Mediated by Matrix metalloproteinase-9

Endocrinology. 1999 Apr;140(4):1657-64. doi: 10.1210/endo.140.4.6623.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / enzymology
  • Breast Neoplasms / pathology*
  • Cell Membrane / enzymology
  • Cell Movement*
  • Collagenases / analysis
  • Collagenases / genetics
  • Collagenases / metabolism*
  • Culture Media, Conditioned
  • Humans
  • Insulin-Like Growth Factor I / pharmacology*
  • Integrins / metabolism
  • Matrix Metalloproteinase 9
  • Neoplasm Invasiveness*
  • Phenylalanine / analogs & derivatives
  • Phenylalanine / pharmacology
  • Polymerase Chain Reaction
  • Protease Inhibitors / pharmacology
  • RNA, Messenger / analysis
  • Receptors, Vitronectin*
  • Thiophenes / pharmacology
  • Tumor Cells, Cultured

Substances

  • Culture Media, Conditioned
  • Integrins
  • Protease Inhibitors
  • RNA, Messenger
  • Receptors, Vitronectin
  • Thiophenes
  • integrin alphaVbeta5
  • Phenylalanine
  • Insulin-Like Growth Factor I
  • batimastat
  • Collagenases
  • Matrix Metalloproteinase 9