TY - JOUR
T1 - Knocking down nucleolin expression in gliomas inhibits tumor growth and induces cell cycle arrest
AU - Xu, Zhiqiang
AU - Joshi, Neel
AU - Agarwal, Ashima
AU - Dahiya, Sonika
AU - Bittner, Patrice
AU - Smith, Erin
AU - Taylor, Sara
AU - Piwnica-Worms, David
AU - Weber, Jason
AU - Leonard, Jeffrey R.
N1 - Funding Information:
Acknowledgments This research was supported in part by the Children’s Discovery Institute (MC-LI-2009-03R, JRL) and by P50 CA94056 (DPW).
PY - 2012/5
Y1 - 2012/5
N2 - 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.
AB - 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.
KW - Astrocytoma
KW - Brain cancer
KW - Pediatric
UR - http://www.scopus.com/inward/record.url?scp=84862783263&partnerID=8YFLogxK
U2 - 10.1007/s11060-012-0827-2
DO - 10.1007/s11060-012-0827-2
M3 - Article
C2 - 22382782
AN - SCOPUS:84862783263
SN - 0167-594X
VL - 108
SP - 59
EP - 67
JO - Journal of Neuro-Oncology
JF - Journal of Neuro-Oncology
IS - 1
ER -