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Search: WFRF:(Wu QL)

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  • Hamerlik, P, et al. (author)
  • Autocrine VEGF-VEGFR2-Neuropilin-1 signaling promotes glioma stem-like cell viability and tumor growth
  • 2012
  • In: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 209:3, s. 507-520
  • Journal article (peer-reviewed)abstract
    • Although vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2) is traditionally regarded as an endothelial cell protein, evidence suggests that VEGFRs may be expressed by cancer cells. Glioblastoma multiforme (GBM) is a lethal cancer characterized by florid vascularization and aberrantly elevated VEGF. Antiangiogenic therapy with the humanized VEGF antibody bevacizumab reduces GBM tumor growth; however, the clinical benefits are transient and invariably followed by tumor recurrence. In this study, we show that VEGFR2 is preferentially expressed on the cell surface of the CD133+ human glioma stem-like cells (GSCs), whose viability, self-renewal, and tumorigenicity rely, at least in part, on signaling through the VEGF-VEGFR2–Neuropilin-1 (NRP1) axis. We find that the limited impact of bevacizumab-mediated VEGF blockage may reflect ongoing autocrine signaling through VEGF–VEGFR2–NRP1, which is associated with VEGFR2–NRP1 recycling and a pool of active VEGFR2 within a cytosolic compartment of a subset of human GBM cells. Whereas bevacizumab failed to inhibit prosurvival effects of VEGFR2-mediated signaling, GSC viability under unperturbed or radiation-evoked stress conditions was attenuated by direct inhibition of VEGFR2 tyrosine kinase activity and/or shRNA-mediated knockdown of VEGFR2 or NRP1. We propose that direct inhibition of VEGFR2 kinase may block the highly dynamic VEGF–VEGFR2–NRP1 pathway and inspire a GBM treatment strategy to complement the currently prevalent ligand neutralization approach.
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  • Result 1-19 of 19
Type of publication
journal article (19)
Type of content
peer-reviewed (19)
Author/Editor
ERNBERG, I (5)
Li, YH (4)
Zhang, Y. (2)
Sun, J. (2)
Cheng, G. (2)
Agerberth, B (2)
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Wang, HY (2)
Huang, LX (2)
Bai, Y. (1)
Wang, X. (1)
Yang, Y. (1)
Zhang, L. (1)
Zhou, L. (1)
Zhuang, X. (1)
Xie, Y. (1)
Hussain, N. (1)
Wu, Z. (1)
Das, S. (1)
Li, Q. (1)
Winblad, B (1)
Xu, Y. (1)
Lee, M (1)
Wang, JY (1)
Zhang, YQ (1)
Liao, J. (1)
Xu, W (1)
Chen, J. (1)
Huang, Z. (1)
Lu, Y (1)
Jin, H. (1)
Tian, Z. (1)
Holmdahl, R (1)
Xia, J. (1)
Xu, J (1)
Wang, B. (1)
Liu, F. (1)
Sun, F (1)
Han, Y (1)
Chen, F (1)
Wu, J (1)
Wang, SF (1)
Ruas, JL (1)
Jannig, PR (1)
Harris, R (1)
Zhang, XL (1)
Chen, YJ (1)
Liu, YJ (1)
Dai, W (1)
Wang, XS (1)
Liu, P. (1)
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University
Karolinska Institutet (19)
Language
English (19)

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