title: A Synthetic Polymer Scaffold Reveals the Self-Maintenance Strategies of Rat Glioma Stem Cells by Organization of the Advantageous Niche.
abstract: 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. Stem Cells 2016;34:1151-1162.
authors.affiliation: Department of Stem Cell Regulation, Medical Research Institute, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
authors.forename: Kouichi
authors.initials: K
authors.lastname: Tabu
authors.affiliation: Department of Stem Cell Regulation, Medical Research Institute, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
authors.forename: Nozomi
authors.initials: N
authors.lastname: Muramatsu
authors.affiliation: EaStChem, School of Chemistry, University of Edinburgh, Edinburgh, London, United Kingdom.
authors.forename: Christian
authors.initials: C
authors.lastname: Mangani
authors.affiliation: EaStChem, School of Chemistry, University of Edinburgh, Edinburgh, London, United Kingdom.
authors.forename: Mei
authors.initials: M
authors.lastname: Wu
authors.affiliation: EaStChem, School of Chemistry, University of Edinburgh, Edinburgh, London, United Kingdom.|School of Materials Science and Engineering, Changzhou University, Changzhou, Jiangsu, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Laboratory of Cancer Research, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Taichi
authors.initials: T
authors.lastname: Kimura
authors.affiliation: Department of Stem Cell Regulation, Medical Research Institute, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Terashima
authors.affiliation: Department of Stem Cell Regulation, Medical Research Institute, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
authors.forename: Norihisa
authors.initials: N
authors.lastname: Bizen
authors.affiliation: Department of Stem Cell Regulation, Medical Research Institute, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Kimura
authors.affiliation: Department of Stem Cell Regulation, Medical Research Institute, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
authors.forename: Wenqian
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Stem Cell Regulation, Medical Research Institute, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Murota
authors.affiliation: Department of Stem Cell Regulation, Medical Research Institute, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kokubu
authors.affiliation: Department of Stem Cell Regulation, Medical Research Institute, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
authors.forename: Ikuo
authors.initials: I
authors.lastname: Nobuhisa
authors.affiliation: Department of Stem Cell Regulation, Medical Research Institute, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
authors.forename: Tetsushi
authors.initials: T
authors.lastname: Kagawa
authors.affiliation: Division of Hematological Malignancy, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: Issay
authors.initials: I
authors.lastname: Kitabayashi
authors.affiliation: EaStChem, School of Chemistry, University of Edinburgh, Edinburgh, London, United Kingdom.
authors.forename: Mark
authors.initials: M
authors.lastname: Bradley
authors.affiliation: Department of Stem Cell Regulation, Medical Research Institute, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Taga
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics / Q000473:pathology*; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005910:Glioma / Q000235:genetics / Q000473:pathology*; D006801:Humans; D007501:Iron / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011108:Polymers / Q000494:pharmacology*; D011140:Polyurethanes / Q000494:pharmacology; D051381:Rats; D051117:Scavenger Receptors, Class A / Q000235:genetics / Q000378:metabolism; D058985:Side-Population Cells / Q000166:cytology / Q000187:drug effects; D055153:Stem Cell Niche / Q000187:drug effects / Q000235:genetics; D054457:Tissue Scaffolds / Q000737:chemistry*; D014168:Transferrin / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: C495139:MSR1 protein, human; D011108:Polymers; D011140:Polyurethanes; D051117:Scavenger Receptors, Class A; D014168:Transferrin; D007501:Iron
keywords: Cancer stem cells; Extracellular matrix; Glioma; Macrophages; Polymers; Stem cell niche