Journal of Neuro-Oncology

, Volume 108, Issue 1, pp 59–67 | Cite as

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. LeonardEmail author
Laboratory Investigation


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.


Astrocytoma Pediatric Brain cancer 



This research was supported in part by the Children’s Discovery Institute (MC-LI-2009-03R, JRL) and by P50 CA94056 (DPW).

Conflicts of interest



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Copyright information

© Springer Science+Business Media, LLC. 2012

Authors and Affiliations

  • Zhiqiang Xu
    • 1
  • Neel Joshi
    • 1
  • Ashima Agarwal
    • 2
  • Sonika Dahiya
    • 2
  • Patrice Bittner
    • 1
  • Erin Smith
    • 3
  • Sara Taylor
    • 1
  • David Piwnica-Worms
    • 3
    • 4
    • 6
  • Jason Weber
    • 3
    • 5
  • Jeffrey R. Leonard
    • 1
    • 7
    Email author
  1. 1.Department of Neurological SurgeryWashington University School of MedicineSt. LouisUSA
  2. 2.Department of Pathology and ImmunologyWashington University School of MedicineSt. LouisUSA
  3. 3.BRIGHT InstituteWashington University School of MedicineSt. LouisUSA
  4. 4.Departments of Cell Biology and PhysiologyWashington University School of MedicineSt. LouisUSA
  5. 5.Department of Internal MedicineWashington University School of MedicineSt. LouisUSA
  6. 6.Department of RadiologyWashington University School of MedicineSt. LouisUSA
  7. 7.Department of PediatricsWashington University School of MedicineSt. LouisUSA

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