PMID- 17369861
OWN - NLM
STAT- MEDLINE
DCOM- 20070928
LR  - 20181113
IS  - 0950-9232 (Print)
IS  - 1476-5594 (Electronic)
IS  - 0950-9232 (Linking)
VI  - 26
IP  - 38
DP  - 2007 Aug 16
TI  - Neuropilin-1 promotes human glioma progression through potentiating the activity 
      of the HGF/SF autocrine pathway.
PG  - 5577-86
AB  - 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.
FAU - Hu, B
AU  - Hu B
AD  - University of Pittsburgh Cancer Institute & Department of Pathology, Pittsburgh, 
      PA 15213-1863, USA. hub@upmc.edu
FAU - Guo, P
AU  - Guo P
FAU - Bar-Joseph, I
AU  - Bar-Joseph I
FAU - Imanishi, Y
AU  - Imanishi Y
FAU - Jarzynka, M J
AU  - Jarzynka MJ
FAU - Bogler, O
AU  - Bogler O
FAU - Mikkelsen, T
AU  - Mikkelsen T
FAU - Hirose, T
AU  - Hirose T
FAU - Nishikawa, R
AU  - Nishikawa R
FAU - Cheng, S Y
AU  - Cheng SY
LA  - eng
GR  - R01 CA102011/CA/NCI NIH HHS/United States
GR  - CA095809/CA/NCI NIH HHS/United States
GR  - R01 CA102011-03/CA/NCI NIH HHS/United States
GR  - R01 CA130966/CA/NCI NIH HHS/United States
GR  - R01 CA102011-04/CA/NCI NIH HHS/United States
GR  - R24 CA095809/CA/NCI NIH HHS/United States
GR  - R01 CA130966-01A1/CA/NCI NIH HHS/United States
GR  - CA102011/CA/NCI NIH HHS/United States
GR  - R01 CA102011-02/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20070319
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Butadienes)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Nitriles)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (U 0126)
RN  - 144713-63-3 (Neuropilin-1)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
SB  - IM
MH  - Animals
MH  - Butadienes/pharmacology
MH  - Cell Line
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Disease Progression
MH  - Enzyme Inhibitors/pharmacology
MH  - Extracellular Signal-Regulated MAP Kinases/antagonists & inhibitors/metabolism
MH  - Gene Expression Regulation, Neoplastic
MH  - Glioma/genetics/metabolism/*pathology
MH  - Hepatocyte Growth Factor/pharmacology/*physiology
MH  - Humans
MH  - Immunoblotting
MH  - Mice
MH  - Neoplasms, Experimental/genetics/metabolism/pathology
MH  - Neovascularization, Pathologic/genetics/metabolism/pathology
MH  - Neuropilin-1/genetics/metabolism/*physiology
MH  - Nitriles/pharmacology
MH  - Phosphorylation/drug effects
MH  - Proto-Oncogene Proteins c-met/physiology
MH  - RNA, Small Interfering/genetics
MH  - Signal Transduction/*physiology
MH  - Transfection
MH  - Transplantation, Heterologous
MH  - Tumor Burden
PMC - PMC2846324
MID - NIHMS183991
EDAT- 2007/03/21 09:00
MHDA- 2007/09/29 09:00
PMCR- 2010/03/27
CRDT- 2007/03/21 09:00
PHST- 2007/03/21 09:00 [pubmed]
PHST- 2007/09/29 09:00 [medline]
PHST- 2007/03/21 09:00 [entrez]
PHST- 2010/03/27 00:00 [pmc-release]
AID - 1210348 [pii]
AID - 10.1038/sj.onc.1210348 [doi]
PST - ppublish
SO  - Oncogene. 2007 Aug 16;26(38):5577-86. doi: 10.1038/sj.onc.1210348. Epub 2007 Mar 
      19.