TY - JOUR
T1 - Targeting of replicating CD133 and OCT4/SOX2 expressing glioma stem cells selects a cell population that reinitiates tumors upon release of therapeutic pressure
AU - Guerra-Rebollo, Marta
AU - Garrido, Cristina
AU - Sánchez-Cid, Lourdes
AU - Soler-Botija, Carolina
AU - Meca-Cortés, Oscar
AU - Rubio, Nuria
AU - Blanco, Jerónimo
N1 - Funding Information:
This work was supported by MINECO/FEDER (SAF2015-64927-C2-1-R) and the Instituto de Salud Carlos III (Red Temática de Investigación Cooperativa en Terapia Celular-TERCEL) and CIBER Cardiovascular -(CB16/11/00403) as part of the Plan Nacional de I + D + I cofounded by ISCIII-Sudirección General de Evaluación y el Fondo Europeo de Desarrollo Regional (FEDER).
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - The existence of radio- and chemotherapy-surviving cancer stem cells is currently believed to explain the inefficacy of anti-glioblastoma (GBM) therapies. The aim of this study was to determine if a therapeutic strategy specifically targeting GBM stem cells (GSC) would completely eradicate a GBM tumor. In both the in vitro and the in vivo models, ganciclovir therapy targeting proliferating GSC promotes the survival of a quiescent, stem-like cell pool capable of reproducing the tumor upon release of the therapeutic pressure. Images of small niches of therapy-surviving tumor cells show organized networks of vascular-like structures formed by tumor cells expressing CD133 or OCT4/SOX2. These results prompted the investigation of tumor cells differentiated to endothelial and pericytic lineages as a potential reservoir of tumor-initiating capacity. Isolated tumor cells with pericyte and endothelial cell lineage characteristics, grown under tumorsphere forming conditions and were able to reproduce tumors after implantation in mice.
AB - The existence of radio- and chemotherapy-surviving cancer stem cells is currently believed to explain the inefficacy of anti-glioblastoma (GBM) therapies. The aim of this study was to determine if a therapeutic strategy specifically targeting GBM stem cells (GSC) would completely eradicate a GBM tumor. In both the in vitro and the in vivo models, ganciclovir therapy targeting proliferating GSC promotes the survival of a quiescent, stem-like cell pool capable of reproducing the tumor upon release of the therapeutic pressure. Images of small niches of therapy-surviving tumor cells show organized networks of vascular-like structures formed by tumor cells expressing CD133 or OCT4/SOX2. These results prompted the investigation of tumor cells differentiated to endothelial and pericytic lineages as a potential reservoir of tumor-initiating capacity. Isolated tumor cells with pericyte and endothelial cell lineage characteristics, grown under tumorsphere forming conditions and were able to reproduce tumors after implantation in mice.
KW - Mesenchymal stromal cells
KW - Endothelial differentiation
KW - Initiating cells
KW - Glioblastoma
KW - Vascularization
KW - Angiogenesis
KW - Growth
KW - Niche
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UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=pure_univeritat_ramon_llull&SrcAuth=WosAPI&KeyUT=WOS:000473417000040&DestLinkType=FullRecord&DestApp=WOS_CPL
U2 - 10.1038/s41598-019-46014-0
DO - 10.1038/s41598-019-46014-0
M3 - Article
C2 - 31267022
AN - SCOPUS:85069267024
SN - 2045-2322
VL - 9
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 9549
ER -
