Neuroepithelial stem cell marker nestin regulates the migration, invasion and growth of human gliomas

  • Authors:
    • Toshiyuki Ishiwata
    • Kiyoshi Teduka
    • Tetsushi Yamamoto
    • Kiyoko Kawahara
    • Yoko Matsuda
    • Zenya Naito
  • Corresponding author:
  • View Affiliations

  • Published online on: Friday, April 15, 2011
  • Pages: 91-99 DOI: 10.3892/or.2011.1267

Abstract

Nestin, a class VI intermediate filament protein, was originally described as a neuronal stem cell marker during central nervous system development. Nestin is expressed in gliomas, and its expression levels are higher in gliomas with high WHO histopathological classification grades than in those with low grades. In the present study, we examined whether nestin regulates the biological activities of human glioma cells. Immunohistochemically, the nestin expression patterns in 10 human glioblastoma patients were examined. The expression levels of nestin in A172, a human high-grade glioma cell line, and KG-1-C, a human low-grade glioma cell line, were examined using real-time PCR, Western blot and immunofluorescence analyses. An expression vector carrying a short hairpin RNA targeting nestin was stably transfected into A172 (Sh) cells. The effects of decreased expression levels of nestin in Sh cells on cell growth, migration, invasion, adhesion to extracellular matrices and fibrillar actin expression on three-dimensional culture plates were examined. The nestin expression vector was transiently transfected into KG-1-C (Nes) cells, and the effects of the nestin overexpression on cell growth and migration were examined. Nestin was expressed in the cytoplasm of the glioblastoma cells in all cases examined. Sh cells showed marked decreases in the expression levels of nestin mRNA and protein, and the growth rate of Sh cells was lower than that of sham (Sc) cells. In contrast, the adhesion activity of Sh cells to types I and IV collagens, fibronectin and laminin was higher than that of Sc cells. Fibrillar actin was clearly detected at the periphery of colonies of Sh cells at the attachment sites on three-dimensional culture plates. The migration and invasion of Sh cells were markedly inhibited compared with those of Sc cells. In contrast, the levels of nestin expression markedly increased in the Nes cells, which were transiently transfected with the nestin expression vector. The growth rate and motility of Nes cells were higher than those of the mock cells. In conclusion, nestin plays important roles in cell growth, migration, invasion and adhesion to extra-cellular matrices in glioma cells. Nestin may serve as a novel candidate for molecular-targeted therapy for gliomas, including glioblastomas.
Journal Cover

July 2011
Volume 26 Issue 1

Print ISSN: 1021-335X
Online ISSN:1791-2431

2013 Impact Factor: 2.191
2014 I.F. (Expected) ≥ 2.527 Ranked #33/202 Oncology
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APA
Ishiwata, T., Teduka, K., Yamamoto, T., Kawahara, K., Matsuda, Y., & Naito, Z. (2011). Neuroepithelial stem cell marker nestin regulates the migration, invasion and growth of human gliomas. Oncology Reports, 26, 91-99. http://dx.doi.org/10.3892/or.2011.1267
MLA
Ishiwata, T., Teduka, K., Yamamoto, T., Kawahara, K., Matsuda, Y., Naito, Z."Neuroepithelial stem cell marker nestin regulates the migration, invasion and growth of human gliomas". Oncology Reports 26.1 (2011): 91-99.
Chicago
Ishiwata, T., Teduka, K., Yamamoto, T., Kawahara, K., Matsuda, Y., Naito, Z."Neuroepithelial stem cell marker nestin regulates the migration, invasion and growth of human gliomas". Oncology Reports 26, no. 1 (2011): 91-99. http://dx.doi.org/10.3892/or.2011.1267