Inhibition of Nodal suppresses angiogenesis and growth of human gliomas

Dueng Yuan Hueng, Gu Jiun Lin, Shing Hwa Huang, Li Wen Liu, Da Tong Ju, Yuan Wu Chen, Huey Kang Sytwu, Chen Chang, Shih Ming Huang, Yi Shian Yeh, Horng Mo Lee, Hsin I. Ma

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Angiogenesis is the hallmark of malignant gliomas positively correlated with the vascular endothelial growth factor (VEGF) expression. We previously reported that expression levels of Nodal, a member of transforming growth factor-β super family, correlate with the malignant invasive behavior of human glioma cells. In this study, we show that knockdown of Nodal suppresses glioma angiogenesis by inhibition of VEGF. In human primary glioma specimens, expression of Nodal positively correlates with WHO glioma tumor grades and expression of VEGF in the corresponding glioma specimens. In human U87MG glioma cells, knockdown of endogenous Nodal by RNA interference (RNAi) significantly decreases colony formation and secretion of VEGF. In vivo, cellular depletion of Nodal in U87MG inhibited brain glioma growth and prolonged the survival of mice with U87MG/shNodal glioma compared with controls. Inhibition of Nodal suppressed tumor vessel growth in U87MG gliomas. Using Nodal inhibitor (SB431542), silencing Nodal, or overexpressing Nodal in the U87MG, GBM8401, and GBM glioma cells, our further experiments revealed that Nodal-induced VEGF expression might, at least in part, mediate through the ERK1/2-HIF-1α- mediated signaling pathway. Taken together, our data revealed that alteration of Nodal expression in glioma cells resulted in changes to VEGF secretion, and subsequent colony formation, in vivo tumor growth, and angiogenesis, all of which are consistent with the regulation of VEGF through the ERK1/2-HIF-1α-mediated signaling, suggesting that Nodal may serve as a potential therapeutic target for the treatment of human gliomas.

Original languageEnglish
Pages (from-to)21-31
Number of pages11
JournalJournal of Neuro-Oncology
Volume104
Issue number1
DOIs
Publication statusPublished - Aug 2011

Keywords

  • CD31
  • ERK1/2
  • HIF-1α
  • Nodal
  • RNA interference
  • VEGF

ASJC Scopus subject areas

  • Clinical Neurology
  • Cancer Research
  • Oncology
  • Neurology

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  • Cite this

    Hueng, D. Y., Lin, G. J., Huang, S. H., Liu, L. W., Ju, D. T., Chen, Y. W., Sytwu, H. K., Chang, C., Huang, S. M., Yeh, Y. S., Lee, H. M., & Ma, H. I. (2011). Inhibition of Nodal suppresses angiogenesis and growth of human gliomas. Journal of Neuro-Oncology, 104(1), 21-31. https://doi.org/10.1007/s11060-010-0467-3