Differential expression of laminin and fibronectin and of their related metalloproteinases in human glioma cell lines: relation to invasion

Neurosci Lett. 2001 Feb 16;299(1-2):140-4. doi: 10.1016/s0304-3940(00)01787-0.

Abstract

In the present work, we analyzed the expression of two major components of the extracellular matrix (ECM), laminin and fibronectin and of two related matrix-metalloproteinases, MMP-2 and MMP-9, in three human glioma cell lines (8 MG, 42 Mg and GL-15) in relation with their differential invasive properties. Immunocytochemistry and Western-blots assays indicated the presence of a 200 kDa laminin, similarly expressed in the three cell lines but undetectable in their ECM. In the opposite, a 230 kDa fibronectin, detected in the three cell lines was differently expressed and only observed in the ECM of the less invasive 8 and 42 MG cells. MMP-2 mRNA analyzed by Northern blots and proMMP-2, evaluated by zymography, were found in the three cell lines but were both ten times higher in the most invasive GL-15 cells. In addition, the active form of MMP-2 was only found in the GL-15 cells. In the opposite, the expression of specific tissular inhibitor (TIMP)-2, an endogenous MMP-2 inhibitor, was restricted to the less invasive cells. MMP-9 activity was detected only in the 8 and 42 MG cells and may not be directly involved in invasion. Taken together, these results indicate that a high MMP-2/TIMP-2 ratio may be responsible for the absence of extracellular fibronectin, underlining the participation of tumour cells in the proteolytic degradation of the ECM. An unbalanced MMP-2/TIMP-2 ratio in the micro-environment of malignant cells may contribute to their invasive properties.

MeSH terms

  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology
  • Brain Neoplasms / physiopathology
  • Extracellular Matrix / metabolism
  • Fibronectins / metabolism*
  • Glioma / metabolism*
  • Glioma / pathology
  • Glioma / physiopathology
  • Humans
  • Laminin / metabolism*
  • Matrix Metalloproteinase 2 / metabolism
  • Metalloendopeptidases / metabolism*
  • Neoplasm Invasiveness / pathology
  • Neoplasm Invasiveness / physiopathology*
  • Tissue Inhibitor of Metalloproteinase-2 / metabolism
  • Tumor Cells, Cultured / metabolism*

Substances

  • Fibronectins
  • Laminin
  • Tissue Inhibitor of Metalloproteinase-2
  • Metalloendopeptidases
  • Matrix Metalloproteinase 2