TY - JOUR
T1 - A Synthetic Polymer Scaffold Reveals the Self-Maintenance Strategies of Rat Glioma Stem Cells by Organization of the Advantageous Niche
AU - Tabu, Kouichi
AU - Muramatsu, Nozomi
AU - Mangani, Christian
AU - Wu, Mei
AU - Zhang, Rong
AU - Kimura, Taichi
AU - Terashima, Kazuo
AU - Bizen, Norihisa
AU - Kimura, Ryosuke
AU - Wang, Wenqian
AU - Murota, Yoshitaka
AU - Kokubu, Yasuhiro
AU - Nobuhisa, Ikuo
AU - Kagawa, Tetsushi
AU - Kitabayashi, Issay
AU - Bradley, Mark
AU - Taga, Tetsuya
N1 - Publisher Copyright:
© 2016 AlphaMed Press.
PY - 2016/5/1
Y1 - 2016/5/1
N2 - Cancer stem cells (CSCs) are believed to be maintained within a microenvironmental niche. Here we used polymer microarrays for the rapid and efficient identification of glioma CSC (GSC) niche mimicries and identified a urethane-based synthetic polymer, upon which two groups of niche components, namely extracellular matrices (ECMs) and iron are revealed. In cultures, side population (SP) cells, defined as GSCs in the rat C6 glioma cell line, are more efficiently sustained in the presence of their differentiated progenies expressing higher levels of ECMs and transferrin, while in xenografts, ECMs are supplied by the vascular endothelial cells (VECs), including SP cell-derived ones with distinctively greater ability to retain xenobiotics than host VECs. Iron is stored in tumor infiltrating host macrophages (Mφs), whose protumoral activity is potently enhanced by SP cell-secreted soluble factor(s). Finally, coexpression of ECM-, iron-, and Mφ-related genes is found to be predictive of glioma patients' outcome. Our polymer-based approach reveals the intrinsic capacities of GSCs, to adapt the environment to organize a self-advantageous microenvironment niche, for their maintenance and expansion, which redefines the current concept of anti-CSC niche therapy and has the potential to accelerate cancer therapy development.
AB - Cancer stem cells (CSCs) are believed to be maintained within a microenvironmental niche. Here we used polymer microarrays for the rapid and efficient identification of glioma CSC (GSC) niche mimicries and identified a urethane-based synthetic polymer, upon which two groups of niche components, namely extracellular matrices (ECMs) and iron are revealed. In cultures, side population (SP) cells, defined as GSCs in the rat C6 glioma cell line, are more efficiently sustained in the presence of their differentiated progenies expressing higher levels of ECMs and transferrin, while in xenografts, ECMs are supplied by the vascular endothelial cells (VECs), including SP cell-derived ones with distinctively greater ability to retain xenobiotics than host VECs. Iron is stored in tumor infiltrating host macrophages (Mφs), whose protumoral activity is potently enhanced by SP cell-secreted soluble factor(s). Finally, coexpression of ECM-, iron-, and Mφ-related genes is found to be predictive of glioma patients' outcome. Our polymer-based approach reveals the intrinsic capacities of GSCs, to adapt the environment to organize a self-advantageous microenvironment niche, for their maintenance and expansion, which redefines the current concept of anti-CSC niche therapy and has the potential to accelerate cancer therapy development.
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U2 - 10.1002/stem.2299
DO - 10.1002/stem.2299
M3 - Article
C2 - 26822103
AN - SCOPUS:84959097873
SN - 1066-5099
VL - 34
SP - 1151
EP - 1162
JO - Stem Cells
JF - Stem Cells
IS - 5
ER -