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PMID: 17369861 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Neuropilin-1 promotes human glioma progression through potentiating the activity of the HGF/SF autocrine pathway.

Oncogene ·Vol. 26 ·No. 38 ·2007-08-16 ·Pages 5577-86

Hu B, Guo P, Bar-Joseph I, Imanishi Y, Jarzynka MJ, Bogler O, Mikkelsen T, Hirose T, Nishikawa R, Cheng SY

Abstract

Neuropilin-1 (NRP1) functions as a coreceptor through interaction with plexin A1 or vascular endothelial growth factor (VEGF) receptor during neuronal development and angiogenesis. NRP1 potentiates the signaling pathways stimulated by semaphorin 3A and VEGF-A in neuronal and endothelial cells, respectively. In this study, we investigate the role of tumor cell-expressed NRP1 in glioma progression. Analyses of human glioma specimens (WHO grade I-IV tumors) revealed a significant correlation of NRP1 expression with glioma progression. In tumor xenografts, overexpression of NRP1 by U87MG gliomas strongly promoted tumor growth and angiogenesis. Overexpression of NRP1 by U87MG cells stimulated cell survival through the enhancement of autocrine hepatocyte growth factor/scatter factor (HGF/SF)/c-Met signaling. NRP1 not only potentiated the activity of endogenous HGF/SF on glioma cell survival but also enhanced HGF/SF-promoted cell proliferation. Inhibition of HGF/SF, c-Met and NRP1 abrogated NRP1-potentiated autocrine HGF/SF stimulation. Furthermore, increased phosphorylation of c-Met correlated with glioma progression in human glioma biopsies in which NRP1 is upregulated and in U87MG NRP1-overexpressing tumors. Together, these data suggest that tumor cell-expressed NRP1 promotes glioma progression through potentiating the activity of the HGF/SF autocrine c-Met signaling pathway, in addition to enhancing angiogenesis, suggesting a novel mechanism of NRP1 in promoting human glioma progression.

MeSH Terms
Animals Butadienes/pharmacology Cell Line Cell Line, Tumor Cell Proliferation/drug effects Disease Progression Enzyme Inhibitors/pharmacology Extracellular Signal-Regulated MAP Kinases/antagonists & inhibitors,metabolism Gene Expression Regulation, Neoplastic Glioma/genetics,metabolism,pathology Hepatocyte Growth Factor/pharmacology,physiology Humans Immunoblotting Mice Neoplasms, Experimental/genetics,metabolism,pathology Neovascularization, Pathologic/genetics,metabolism,pathology Neuropilin-1/genetics,metabolism,physiology Nitriles/pharmacology Phosphorylation/drug effects Proto-Oncogene Proteins c-met/physiology RNA, Small Interfering/genetics Signal Transduction/physiology Transfection Transplantation, Heterologous Tumor Burden
Chemicals
Butadienes Enzyme Inhibitors Nitriles RNA, Small Interfering U 0126 Neuropilin-1 Hepatocyte Growth Factor Proto-Oncogene Proteins c-met Extracellular Signal-Regulated MAP Kinases
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Hu B
University of Pittsburgh Cancer Institute & Department of Pathology, Pittsburgh, PA 15213-1863, USA. hub@upmc.edu
Guo P
Bar-Joseph I
Imanishi Y
Jarzynka M J
Bogler O
Mikkelsen T
Hirose T
Nishikawa R
Cheng S Y
References (17)
17 references, click to expand
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Article Info
Journal
Oncogene
Abbr.
Oncogene
ISSN
0950-9232
DOI
10.1038/sj.onc.1210348
Email
hub@upmc.edu
Published
2007-08-16
Epub
2007-00-19
Pages
5577-86
Language
English
Region
England
NLM ID
8711562
PMCID
PMC2846324
Subset
IM
Grants
NCI NIH HHS · R01 CA102011 · United States
NCI NIH HHS · CA095809 · United States
NCI NIH HHS · R01 CA102011-03 · United States
NCI NIH HHS · R01 CA130966 · United States
NCI NIH HHS · R01 CA102011-04 · United States
NCI NIH HHS · R24 CA095809 · United States
NCI NIH HHS · R01 CA130966-01A1 · United States
NCI NIH HHS · CA102011 · United States
NCI NIH HHS · R01 CA102011-02 · United States
External Links
PubMed source DOI: 10.1038/sj.onc.1210348 PMC Full Text View journal details
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