A Synthetic Polymer Scaffold Reveals the Self-Maintenance Strategies of Rat Glioma Stem Cells by Organization of the Advantageous Niche

Kouichi Tabu, Nozomi Muramatsu, Christian Mangani, Mei Wu, Rong Zhang, Taichi Kimura, Kazuo Terashima, Norihisa Bizen, Ryosuke Kimura, Wenqian Wang, Yoshitaka Murota, Yasuhiro Kokubu, Ikuo Nobuhisa, Tetsushi Kagawa, Issay Kitabayashi, Mark Bradley, Tetsuya Taga

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1151-1162
Number of pages12
JournalStem Cells
Volume34
Issue number5
DOIs
Publication statusPublished - 01-05-2016
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General Medicine

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