Matrix metalloproteinase-2 promotes αvβ3 integrin-mediated adhesion and migration of human melanoma cells by cleaving fibronectin

PLoS One. 2012;7(7):e41591. doi: 10.1371/journal.pone.0041591. Epub 2012 Jul 27.

Abstract

Background: Matrix metalloproteinase-2 (MMP-2) is a key regulator in the migration of tumor cells. αvβ3 integrin has been reported to play a critical role in cell adhesion and regulate the migration of tumor cells by promoting MMP-2 activation. However, little is known about the effects of MMP-2 on αvβ3 integrin activity and αvβ3 integrin-mediated adhesion and migration of tumor cells.

Methodology/principal findings: Human melanoma cells were seeded using an agarose drop model and/or subjected to in vitro analysis using immunofluorescence, adhesion, migration and invasion assays to investigate the relationship between active MMP-2 and αvβ3 integrin during the adhesion and migration of the tumor cells. We found that MMP-2 was localized at the leading edge of spreading cells before αvβ3 integrin. αvβ3 integrin-mediated adhesion and migration of the tumor cells were inhibited by a MMP-2 inhibitor. MMP-2 cleaved fibronectin into small fragments, which promoted the adhesion and migration of the tumor cells.

Conclusion/significance: MMP-2 cleaves fibronectin into small fragments to enhance the adhesion and migration of human melanoma cells mediated by αvβ3 integrin. These results indicate that MMP-2 may guide the direction of the tumor cell migration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Adhesion
  • Cell Line, Tumor
  • Cell Movement*
  • Fibronectins / metabolism*
  • Humans
  • Integrin alphaVbeta3 / metabolism*
  • Matrix Metalloproteinase 2 / metabolism*
  • Melanoma / metabolism*
  • Melanoma / pathology
  • Neoplasm Invasiveness

Substances

  • Fibronectins
  • Integrin alphaVbeta3
  • MMP2 protein, human
  • Matrix Metalloproteinase 2

Grant support

This study was supported by grants from the National Nature Science Foundation of China (81071726, 81172014), the specialized Research Fund for the Doctoral Program of Higher education (20100043110007), and the Fundamental Research Funds for the Central Universities (10SSXT129). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.