Antisense human neuroglia related cell adhesion molecule hNr-CAM, reduces the tumorigenic properties of human glioblastoma cells

Anticancer Res. 1999 Nov-Dec;19(6B):4947-53.

Abstract

Background: Human Nr-CAM (Neuroglia related Cell Adhesion Molecule) is over expressed in glioblastoma multiforme tissue (GMT) as compared to normal brain tissue (NBT).

Materials and methods: We transfected a human glioblastoma cell line (2020-CRL) with a vector that overexpresses antisense hNr-CAM using a CMVpromoter.

Results: Antisense hNr- CAM caused reduction in the native hNr-CAM expression, changed cell morphology, reduced the cell proliferation rate and lengthening of the cell cycle. Furthermore, antisense hNr-CAM overexpression in these cells caused extensive reduction in the number of soft agar colonies and invasion through extra cellular matrix (ECM) gel in vitro. Subcutaneous injection of antisense hNr-CAM overexpressing glioblastoma cells into nude mice caused complete inhibition of tumor formation as compared to vector only transfected cells. Intra-tumoral inoculation of antisense hNr-CAM expressing plasmid also caused slow tumor growth in nude mice in vivo.

Conclusion: On the basis of these results, we conclude that hNr-CAM is a valid target for potential gene therapy of glioblastoma tumors.

MeSH terms

  • Animals
  • Base Sequence
  • Brain Neoplasms / pathology*
  • Cell Adhesion Molecules*
  • Cell Adhesion Molecules, Neuronal / genetics*
  • Cell Division
  • Cytomegalovirus / genetics
  • DNA Primers
  • Female
  • Glioblastoma / pathology*
  • Humans
  • Mice
  • Middle Aged
  • Neoplasm Invasiveness
  • Oligonucleotides, Antisense / pharmacology*
  • Plasmids
  • Promoter Regions, Genetic
  • Transfection
  • Tumor Cells, Cultured

Substances

  • Cell Adhesion Molecules
  • Cell Adhesion Molecules, Neuronal
  • DNA Primers
  • NRCAM protein, human
  • Nrcam protein, mouse
  • Oligonucleotides, Antisense