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

• Original Article
• Published: 19 March 2007
• P Guo1,2,
• I Bar-Joseph1,2,
• Y Imanishi1,2,
• M J Jarzynka1,2,
• O Bogler3,
• T Mikkelsen4,
• T Hirose5,
• R Nishikawa6 &
• …
• S Y Cheng1,2

Oncogene volume 26, pages 5577–5586 (2007)Cite this article

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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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Acknowledgements

The work was supported by grants NIH CA102011 and RSG CSM-107144 (S-Y C), the Hillman Fellows Program for Innovative Cancer Research to S-Y C and B H, and grant NIH CA095809 to TM (in part).

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Authors and Affiliations

1. University of Pittsburgh Cancer Institute & Department of Pathology, Pittsburgh, PA, USA
   B Hu, P Guo, I Bar-Joseph, Y Imanishi, M J Jarzynka & S Y Cheng
2. Department of Pathology, Research Pavilion at Hillman Cancer Center, Pittsburgh, PA, USA
   P Guo, I Bar-Joseph, Y Imanishi, M J Jarzynka & S Y Cheng
3. Department of Neurosurgery & Brain Tumor Center, MD Anderson Cancer Center, University of Texas, Houston, TX, USA
   O Bogler
4. Department of Neurosurgery, Hermelin Brain Tumor Center, Henry Ford Hospital, Detroit, MI, USA
   T Mikkelsen
5. Department of Pathology, Saitama Medical University, Saitama, Japan
   T Hirose
6. Department of Neurosurgery, Saitama Medical University, Saitama, Japan
   R Nishikawa

Authors

1. B Hu
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2. P Guo
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3. I Bar-Joseph
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4. Y Imanishi
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5. M J Jarzynka
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6. O Bogler
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7. T Mikkelsen
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8. T Hirose
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9. R Nishikawa
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10. S Y Cheng
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Corresponding authors

Correspondence toB Hu or S Y Cheng.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Hu, B., Guo, P., Bar-Joseph, I. et al. Neuropilin-1 promotes human glioma progression through potentiating the activity of the HGF/SF autocrine pathway.Oncogene 26, 5577–5586 (2007). https://doi.org/10.1038/sj.onc.1210348

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• Received: 18 September 2006
• Revised: 18 December 2006
• Accepted: 06 January 2007
• Published: 19 March 2007
• Issue Date: 16 August 2007
• DOI: https://doi.org/10.1038/sj.onc.1210348

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