Knocking down nucleolin expression in gliomas inhibits tumor growth and induces cell cycle arrest

Zhiqiang Xu, Neel Joshi, Ashima Agarwal, Sonika Dahiya, Patrice Bittner, Erin Smith, Sara Taylor, David Piwnica-Worms, Jason Weber, Jeffrey R. Leonard

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

Abstract

Nucleolin is a multifunctional protein whose expression often correlates with increased cellular proliferation. While the expression of nucleolin is often elevated in numerous cancers, its expression in normal human brain and in astrocytomas has not been previously reported. Using paraffin-embedded sections from normal adult autopsy specimens and glioma resection specimens, we demonstrate that nucleolin expression is limited in the normal human brain specifically to mature neurons, ependymal cells, and granular cells of the dentate gyrus. While astrocytes in the normal human brain do not express nucleolin at significant levels, glioblastoma cell lines and primary human astrocytoma cells exhibit considerable nucleolin expression. Reduction of nucleolin expression through siRNA-mediated knockdown in the U87MG glioblastoma cell line caused a dramatic decrease in cell proliferation and induced cell cycle arrest in vitro. Moreover, conditional siRNA knockdown of nucleolin expression in U87MG intracranial xenografts in nude mice caused dramatic reduction in tumor size. Taken together, these results implicate nucleolin in the regulation of human astrocytoma proliferation in vitro and tumorigenicity in vivo and suggest that nucleolin may represent a potential novel therapeutic target for astrocytomas.

Original languageEnglish
Pages (from-to)59-67
Number of pages9
JournalJournal of Neuro-Oncology
Volume108
Issue number1
DOIs
StatePublished - May 2012

Keywords

  • Astrocytoma
  • Brain cancer
  • Pediatric

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