BCL-2 promotes migration and invasiveness of human glioma cells

FEBS Lett. 1998 Dec 4;440(3):419-24. doi: 10.1016/s0014-5793(98)01494-x.


Malignant progression in gliomas is correlated with increased migratory capacity which involves metalloproteolytic activity. Here, we report that ectopic expression of BCL-2 in two malignant glioma sublines markedly promoted glioma cell migration from spheroids and invasion into Matrigel-coated membranes. Invasion of fetal rat-brain aggregates was enhanced by BCL-2. Zymography revealed activation of matrix metalloproteinase-2 (MMP-2) in BCL-2-expressing cells. BCL-2 expressing cells showed an increase in MMP-2/-3/-12 (LN-18), and MMP-9/-12 and cell surface urokinase-type plasminogen activator (u-PA) (LN-229) mRNA and a reduction in tissue inhibitors of metalloproteinases (TIMP)-2 mRNA (LN-229). Taken together, we propose a novel function for BCL-2 in the malignant phenotype of glioma cells, that is, to enhance migration and invasion by altering the expression of a set of metalloproteinases and their inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Neoplasms / secondary
  • Cell Movement
  • Down-Regulation
  • Gelatinases / metabolism
  • Gene Transfer Techniques
  • Glioma / pathology*
  • Humans
  • Matrix Metalloproteinase 2
  • Metalloendopeptidases / metabolism
  • Neoplasm Invasiveness*
  • Phenotype
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / physiology*
  • Rats
  • Spheroids, Cellular / pathology
  • Tissue Inhibitor of Metalloproteinase-2 / metabolism
  • Tumor Cells, Cultured
  • Up-Regulation
  • Urokinase-Type Plasminogen Activator / metabolism


  • Proto-Oncogene Proteins c-bcl-2
  • Tissue Inhibitor of Metalloproteinase-2
  • Urokinase-Type Plasminogen Activator
  • Gelatinases
  • Metalloendopeptidases
  • Matrix Metalloproteinase 2