Abstract
Human glioblastomas (GBM) are thought to be initiated by glioma stem-like cells (GSLCs). GSLCs also participate in tumor neovascularization by transdifferentiating into vascular endothelial cells. Here, we report a critical role of GSLCs in the formation of vasculogenic mimicry (VM), which defines channels lined by tumor cells to supply nutrients to early growing tumors and tumor initiation. GSLCs preferentially expressed vascular endothelial growth factor receptor-2 (VEGFR-2) that upon activation by VEGF, mediated chemotaxis, tubule formation and increased expression of critical VM markers by GSLCs. Knockdown of VEGFR-2 in GSLCs by shRNA markedly reduced their capacity of self-renewal, forming tubules, initiating xenograft tumors, promoting vascularization and the establishment of VM. Our study demonstrates VEGFR-2 as an essential molecule to sustain the "stemness" of GSLCs, their capacity to initiate tumor vasculature, and direct initiation of tumor.
| Original language | English |
|---|---|
| Article number | e57188 |
| Journal | PLoS One |
| Volume | 8 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Mar 11 2013 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Agricultural and Biological Sciences(all)
- Biochemistry, Genetics and Molecular Biology(all)
- Medicine(all)
Cite this
Vascular Endothelial Growth Factor Receptor 2 (VEGFR-2) Plays a Key Role in Vasculogenic Mimicry Formation, Neovascularization and Tumor Initiation by Glioma Stem-like Cells. / Yao, Xiaohong; Ping, Yifang; Liu, Ying; Chen, Kequiang; Yoshimura, Teizo; Liu, Mingyong; Gong, Wanghua; Chen, Chong; Niu, Qin; Guo, Deyu; Zhang, Xia; Wang, Ji Ming; Bian, Xiuwu.
In: PLoS One, Vol. 8, No. 3, e57188, 11.03.2013.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Vascular Endothelial Growth Factor Receptor 2 (VEGFR-2) Plays a Key Role in Vasculogenic Mimicry Formation, Neovascularization and Tumor Initiation by Glioma Stem-like Cells
AU - Yao, Xiaohong
AU - Ping, Yifang
AU - Liu, Ying
AU - Chen, Kequiang
AU - Yoshimura, Teizo
AU - Liu, Mingyong
AU - Gong, Wanghua
AU - Chen, Chong
AU - Niu, Qin
AU - Guo, Deyu
AU - Zhang, Xia
AU - Wang, Ji Ming
AU - Bian, Xiuwu
PY - 2013/3/11
Y1 - 2013/3/11
N2 - Human glioblastomas (GBM) are thought to be initiated by glioma stem-like cells (GSLCs). GSLCs also participate in tumor neovascularization by transdifferentiating into vascular endothelial cells. Here, we report a critical role of GSLCs in the formation of vasculogenic mimicry (VM), which defines channels lined by tumor cells to supply nutrients to early growing tumors and tumor initiation. GSLCs preferentially expressed vascular endothelial growth factor receptor-2 (VEGFR-2) that upon activation by VEGF, mediated chemotaxis, tubule formation and increased expression of critical VM markers by GSLCs. Knockdown of VEGFR-2 in GSLCs by shRNA markedly reduced their capacity of self-renewal, forming tubules, initiating xenograft tumors, promoting vascularization and the establishment of VM. Our study demonstrates VEGFR-2 as an essential molecule to sustain the "stemness" of GSLCs, their capacity to initiate tumor vasculature, and direct initiation of tumor.
AB - Human glioblastomas (GBM) are thought to be initiated by glioma stem-like cells (GSLCs). GSLCs also participate in tumor neovascularization by transdifferentiating into vascular endothelial cells. Here, we report a critical role of GSLCs in the formation of vasculogenic mimicry (VM), which defines channels lined by tumor cells to supply nutrients to early growing tumors and tumor initiation. GSLCs preferentially expressed vascular endothelial growth factor receptor-2 (VEGFR-2) that upon activation by VEGF, mediated chemotaxis, tubule formation and increased expression of critical VM markers by GSLCs. Knockdown of VEGFR-2 in GSLCs by shRNA markedly reduced their capacity of self-renewal, forming tubules, initiating xenograft tumors, promoting vascularization and the establishment of VM. Our study demonstrates VEGFR-2 as an essential molecule to sustain the "stemness" of GSLCs, their capacity to initiate tumor vasculature, and direct initiation of tumor.
UR - http://www.scopus.com/inward/record.url?scp=84874890917&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84874890917&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0057188
DO - 10.1371/journal.pone.0057188
M3 - Article
C2 - 23536763
AN - SCOPUS:84874890917
VL - 8
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 3
M1 - e57188
ER -