Cancer Cell Biology
Downregulation of laminin α4 chain expression inhibits glioma invasion in vitro and in vivo
Article first published online: 24 MAY 2005
Copyright © 2005 Wiley-Liss, Inc.
International Journal of Cancer
Volume 117, Issue 1, pages 41–50, 20 October 2005
How to Cite
Nagato, S., Nakagawa, K., Harada, H., Kohno, S., Fujiwara, H., Sekiguchi, K., Ohue, S., Iwata, S. and Ohnishi, T. (2005), Downregulation of laminin α4 chain expression inhibits glioma invasion in vitro and in vivo. Int. J. Cancer, 117: 41–50. doi: 10.1002/ijc.21102
- Issue published online: 2 AUG 2005
- Article first published online: 24 MAY 2005
- Manuscript Accepted: 31 JAN 2005
- Manuscript Received: 25 AUG 2004
- Integrated Center of Sciences, Ehime University
- Ministry of Education, Culture, Sports, Science and Technology, Japan. Grant Number: 14571314
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.