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Autocrine VEGF-VEGF...
Autocrine VEGF-VEGFR2-Neuropilin-1 signaling promotes glioma stem-like cell viability and tumor growth
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Hamerlik, P (författare)
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Lathia, JD (författare)
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Rasmussen, R (författare)
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Wu, QL (författare)
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Bartkova, J (författare)
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Lee, M (författare)
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Moudry, P (författare)
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Bartek, J (författare)
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Fischer, W (författare)
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Lukas, J (författare)
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Rich, JN (författare)
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Bartek, J (författare)
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- 2012-03-05
- 2012
- Engelska.
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Ingår i: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 209:3, s. 507-520
- Relaterad länk:
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http://jem.rupress.o...
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http://kipublication...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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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- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Hamerlik, P
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Lathia, JD
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Rasmussen, R
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Wu, QL
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Bartkova, J
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Lee, M
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visa fler...
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Moudry, P
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Bartek, J
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Fischer, W
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Lukas, J
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Rich, JN
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visa färre...
- Artiklar i publikationen
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The Journal of e ...
- Av lärosätet
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Karolinska Institutet