SEARCH

SEARCH BY CITATION

Keywords:

  • glioma;
  • invasion;
  • laminin;
  • antisense

Abstract

The laminin family is a structural constituent of the extracellular matrix that plays an essential role in promoting the motility of infiltrative tumor cells. We investigated the role of laminin α4 chain, a subset of laminin-8, -9 and -14, in the motile and invasive activities of human glioma cells. All malignant glioma cell lines examined expressed more mRNA for the laminin α4 and β1 chains than for the β2 chain, indicating that these cells predominantly express the laminin-8 isoform. Introducing an antisense oligonucleotide for laminin α4 chain (AS-Ln-α4) into the glioma cells resulted in downregulation of laminin α4 expression. AS-Ln-α4 also significantly suppressed glioma cell adhesion and migration. Furthermore, invasiveness was significantly reduced in cells transfected with AS-Ln-α4 compared to those transfected with the sense oligonucleotide (S-Ln-α4). Indeed, when glioma spheroids were implanted into rat brain slices, AS-Ln-α4-transfected cells failed to invade surrounding normal brain tissues. In addition, intracerebral injection of glioma cells transfected with AS-Ln-α4 into nude mice resulted in the formation of a noninvasive tumor, whereas injection of cells transfected with S-Ln-α4 resulted in diffuse invasion of brain tissue. These results suggest that mainly laminin-8 is essential for the invasive activity of human glioma cells; thus, a novel therapeutic strategy could target this molecule to treat patients with malignant glioma. © 2005 Wiley-Liss, Inc.