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

doi:10.1038/sj.onc.1210348

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

Neurology

Research output: Contribution to journal › Article › peer-review

160 Scopus citations

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 language	English (US)
Pages (from-to)	5577-5586
Number of pages	10
Journal	Oncogene
Volume	26
Issue number	38
DOIs	https://doi.org/10.1038/sj.onc.1210348
State	Published - Aug 16 2007

Funding

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).

Keywords

Glioma
HGF/SF
Neuropilin-1
c-Met

ASJC Scopus subject areas

Genetics
Molecular Biology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/sj.onc.1210348

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@article{aca236962ca84a0bb7a9a32f69e745ff,

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

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.",

keywords = "Glioma, HGF/SF, Neuropilin-1, c-Met",

author = "B. Hu and P. Guo and I. Bar-Joseph and Y. Imanishi and Jarzynka, {M. J.} and O. Bogler and T. Mikkelsen and T. Hirose and R. Nishikawa and Cheng, {S. Y.}",

note = "Funding Information: 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).",

year = "2007",

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doi = "10.1038/sj.onc.1210348",

language = "English (US)",

volume = "26",

pages = "5577--5586",

journal = "Oncogene",

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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.

N1 - Funding Information: 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).

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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SN - 0950-9232

VL - 26

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EP - 5586

JO - Oncogene

JF - Oncogene

IS - 38

ER -

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

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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