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

B. Hu*, P. Guo, I. Bar-Joseph, Y. Imanishi, M. J. Jarzynka, O. Bogler, T. Mikkelsen, T. Hirose, R. Nishikawa, S. Y. Cheng

*Corresponding author for this work

Research output: Contribution to journalArticle

130 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)5577-5586
Number of pages10
JournalOncogene
Volume26
Issue number38
DOIs
StatePublished - Aug 16 2007

Fingerprint

Neuropilin-1
Hepatocyte Growth Factor
Glioma
Neoplasms
Cell Survival
Semaphorin-3A
Vascular Endothelial Growth Factor Receptor
Heterografts

Keywords

  • Glioma
  • HGF/SF
  • Neuropilin-1
  • c-Met

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Hu, B. ; Guo, P. ; Bar-Joseph, I. ; Imanishi, Y. ; Jarzynka, M. J. ; Bogler, O. ; Mikkelsen, T. ; Hirose, T. ; Nishikawa, R. ; Cheng, S. Y. / Neuropilin-1 promotes human glioma progression through potentiating the activity of the HGF/SF autocrine pathway. In: Oncogene. 2007 ; Vol. 26, No. 38. pp. 5577-5586.
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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.",
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Hu, B, Guo, P, Bar-Joseph, I, Imanishi, Y, Jarzynka, MJ, Bogler, O, Mikkelsen, T, Hirose, T, Nishikawa, R & Cheng, SY 2007, 'Neuropilin-1 promotes human glioma progression through potentiating the activity of the HGF/SF autocrine pathway', Oncogene, vol. 26, no. 38, pp. 5577-5586. https://doi.org/10.1038/sj.onc.1210348

Neuropilin-1 promotes human glioma progression through potentiating the activity of the HGF/SF autocrine pathway. / Hu, B.; Guo, P.; Bar-Joseph, I.; Imanishi, Y.; Jarzynka, M. J.; Bogler, O.; Mikkelsen, T.; Hirose, T.; Nishikawa, R.; Cheng, S. Y.

In: Oncogene, Vol. 26, No. 38, 16.08.2007, p. 5577-5586.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Neuropilin-1 promotes human glioma progression through potentiating the activity of the HGF/SF autocrine pathway

AU - Hu, B.

AU - Guo, P.

AU - Bar-Joseph, I.

AU - Imanishi, Y.

AU - Jarzynka, M. J.

AU - Bogler, O.

AU - Mikkelsen, T.

AU - Hirose, T.

AU - Nishikawa, R.

AU - Cheng, S. Y.

PY - 2007/8/16

Y1 - 2007/8/16

N2 - 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.

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.

KW - Glioma

KW - HGF/SF

KW - Neuropilin-1

KW - c-Met

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