The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
Endothelial Cells Create a Stem Cell Niche in Glioblastoma by Providing NOTCH Ligands That Nurture Self-Renewal of Cancer Stem-Like Cells
Open accessAbstract
One important function of endothelial cells in glioblastoma multiforme (GBM) is to create a niche that helps promote self-renewal of cancer stem-like cells (CSLC). However, the underlying molecular mechanism for this endothelial function is not known. Since activation of NOTCH signaling has been found to be required for propagation of GBM CSLCs, we hypothesized that the GBM endothelium may provide the source of NOTCH ligands. Here, we report a corroboration of this concept with a demonstration that NOTCH ligands are expressed in endothelial cells adjacent to NESTIN and NOTCH receptor-positive cancer cells in primary GBMs. Coculturing human brain microvascular endothelial cells (hBMEC) or NOTCH ligand with GBM neurospheres promoted GBM cell growth and increased CSLC self-renewal. Notably, RNAi-mediated knockdown of NOTCH ligands in hBMECs abrogated their ability to induce CSLC self-renewal and GBM tumor growth, both in vitro and in vivo. Thus, our findings establish that NOTCH activation in GBM CSLCs is driven by juxtacrine signaling between tumor cells and their surrounding endothelial cells in the tumor microenvironment, suggesting that targeting both CSLCs and their niche may provide a novel strategy to deplete CSLCs and improve GBM treatment. Cancer Res; 71(18); 6061–72. ©2011 AACR.
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Cited by
Cancer stem cells in glioblastoma
Lathia, J. D., Mack, S. C., Mulkearns-Hubert, E. E., Valentim, C. L. L., & Rich, J. N. (2015) · Genes & Development · doi:10.1101/gad.261982.115 · Cited by 1,520
Notch signaling pathway: architecture, disease, and therapeutics
Zhou, B., Lin, W., Long, Y., Yang, Y., Zhang, H., Wu, K., & Chu, Q. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-00934-y · Cited by 1,114
Tackling the cancer stem cells — what challenges do they pose?
Pattabiraman, D. R., & Weinberg, R. A. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4253 · Cited by 990
The Varied Roles of Notch in Cancer
Aster, J. C., Pear, W. S., & Blacklow, S. C. (2017) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-052016-100127 · Cited by 710
Notch Signaling in the Tumor Microenvironment
Meurette, O., & Mehlen, P. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.07.009 · Cited by 678
Metadata
- Authors
- Zhu, T. S., Costello, M. A., Talsma, C. E., Flack, C. G., Crowley, J. G., Hamm, L. L., He, X., Hervey-Jumper, S. L., Heth, J. A., Muraszko, K. M., DiMeco, F., Vescovi, A. L., & Fan, X.
- Venue
- Cancer Research
- Published
- 2011-09-13
- Volume
- 71
- Issue
- 18
- Pages
- 6061-6072
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- OpenAlex
- W2162012621
- Cited by
- 400
- References
- 9
- FWCI
- 13.00
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Zhu, T. S., Costello, M. A., Talsma, C. E., Flack, C. G., Crowley, J. G., Hamm, L. L., He, X., Hervey-Jumper, S. L., Heth, J. A., Muraszko, K. M., DiMeco, F., Vescovi, A. L., & Fan, X. (2011). Endothelial Cells Create a Stem Cell Niche in Glioblastoma by Providing NOTCH Ligands That Nurture Self-Renewal of Cancer Stem-Like Cells. Cancer Research. https://doi.org/10.1158/0008-5472.can-10-4269
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