The DOI matches its Crossref record; 77 of the 77 references it cites were found in a registry or an index.
Autocrine VEGF–VEGFR2–Neuropilin-1 signaling promotes glioma stem-like cell viability and tumor growth
Open accessAbstract
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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Cites
Stem cells, cancer, and cancer stem cells
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Cited by
Goel, H. L., & Mercurio, A. M. (2013) · Nature Reviews Cancer · doi:10.1038/nrc3627 · Cited by 1,253
Unravelling cancer stem cell potential
Beck, B., & Blanpain, C. (2013) · Nature Reviews Cancer · doi:10.1038/nrc3597 · Cited by 905
Cancer Stem Cells: Basic Concepts and Therapeutic Implications
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Cancer stem cells and chemoresistance: The smartest survives the raid
Zhao, J. (2016) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2016.02.008 · Cited by 437
Hypoxia in the glioblastoma microenvironment: shaping the phenotype of cancer stem-like cells
Colwell, N., Larion, M., Giles, A. J., Seldomridge, A. N., Sizdahkhani, S., Gilbert, M. R., & Park, D. M. (2017) · Neuro-Oncology · doi:10.1093/neuonc/now258 · Cited by 284
Metadata
- Authors
- Hamerlik, P., Lathia, J. D., Rasmussen, R., Wu, Q., Bartkova, J., Lee, M., Moudry, P., Bartek, J., Fischer, W., Lukas, J., Rich, J. N., & Bartek, J.
- Venue
- Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2012-03-05
- Volume
- 209
- Issue
- 3
- Pages
- 507-520
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- OpenAlex
- W2166637572
- Cited by
- 406
- References
- 77
- FWCI
- 13.01
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Hamerlik, P., Lathia, J. D., Rasmussen, R., Wu, Q., Bartkova, J., Lee, M., Moudry, P., Bartek, J., Fischer, W., Lukas, J., Rich, J. N., & Bartek, J. (2012). Autocrine VEGF–VEGFR2–Neuropilin-1 signaling promotes glioma stem-like cell viability and tumor growth. Journal of Experimental Medicine. https://doi.org/10.1084/jem.20111424
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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