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Induction of protumoral CD 11c high macrophages by glioma cancer stem cells through GM ‐ CSF
Author(s) -
Kokubu Yasuhiro,
Tabu Kouichi,
Muramatsu Nozomi,
Wang Wenqian,
Murota Yoshitaka,
Nobuhisa Ikuo,
Jinushi Masahisa,
Taga Tetsuya
Publication year - 2016
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/gtc.12333
Subject(s) - cd11c , cancer stem cell , biology , cancer research , glioma , stem cell , population , tumor microenvironment , tumor progression , immune system , cancer cell , transplantation , bone marrow , immunology , cancer , microbiology and biotechnology , medicine , phenotype , gene , biochemistry , genetics , environmental health
Cancer stem cells ( CSC s) 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 ( TAM s) are known to be involved in cancer progression and thus can be a component of CSC niche. Although TAM s are known to play multiple roles in tumor progression, involvement of CSC s in TAM development fully remains to be elucidated. Using rat C6 glioma side population ( SP ) cells as a model of glioma CSC s, we here show that CSC s 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, CD 11c low and CD 11c high cells. Interestingly, only the CD 11c high subset of cells have protumoral activity, as shown by intracranial transplantation into immune‐deficient mice together with CSC s. These CD 11c high macrophages were observed in the tumor formed by co‐transplantation with CSC s. Furthermore, CSC s produced GM ‐ CSF and anti‐ GM ‐ CSF antibody inhibited CSC ‐induced TAM development. In conclusion, CSC s have the ability to self‐create their own niche involving TAM s through CSC ‐derived GM ‐ CSF , which can thus be a therapeutic target in view of CSC niche disruption.