title: Induction of protumoral CD11c(high) macrophages by glioma cancer stem cells through GM-CSF.
abstract: Cancer stem cells (CSCs) are maintained under special microenvironment called niche, and elucidation and targeting of the CSC niche will be a feasible strategy for cancer eradication. Tumor-associated macrophages (TAMs) are known to be involved in cancer progression and thus can be a component of CSC niche. Although TAMs are known to play multiple roles in tumor progression, involvement of CSCs in TAM development fully remains to be elucidated. Using rat C6 glioma side population (SP) cells as a model of glioma CSCs, we here show that CSCs induce the TAM development by promoting survival and differentiation of bone marrow-derived monocytes. CSC-induced macrophages can be separated into two distinct subsets of cells, CD11c(low) and CD11c(high) cells. Interestingly, only the CD11c(high) subset of cells have protumoral activity, as shown by intracranial transplantation into immune-deficient mice together with CSCs. These CD11c(high) macrophages were observed in the tumor formed by co-transplantation with CSCs. Furthermore, CSCs produced GM-CSF and anti-GM-CSF antibody inhibited CSC-induced TAM development. In conclusion, CSCs have the ability to self-create their own niche involving TAMs through CSC-derived GM-CSF, which can thus be a therapeutic target in view of CSC niche disruption.
authors.affiliation: Department of Stem Cell Regulation, Medical Research Institute, Tokyo Medical and Dental University (TMDU), 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8510, 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), 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8510, 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), 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
authors.forename: Nozomi
authors.initials: N
authors.lastname: Muramatsu
authors.affiliation: Department of Stem Cell Regulation, Medical Research Institute, Tokyo Medical and Dental University (TMDU), 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8510, 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), 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8510, 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), 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
authors.forename: Ikuo
authors.initials: I
authors.lastname: Nobuhisa
authors.affiliation: Research Center for Infection-Associated Cancer, Institute for Genetic Medicine, Hokkaido University, Kita 15, Nishi 7, Kita-ku, Sapporo, Hokkaido, 060-0815, Japan.|Institute for Advanced Medical Research, Keio University School of Medicine, Shinano-machi 35, Shinjuku-ku, Tokyo, 160-8582, Japan.
authors.forename: Masahisa
authors.initials: M
authors.lastname: Jinushi
authors.affiliation: Department of Stem Cell Regulation, Medical Research Institute, Tokyo Medical and Dental University (TMDU), 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Taga
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D018845:CD11 Antigens / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D005260:Female; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D009000:Monocytes / Q000166:cytology / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000637:transplantation*; D051381:Rats; D055153:Stem Cell Niche
chemical_list: D018845:CD11 Antigens; D016178:Granulocyte-Macrophage Colony-Stimulating Factor