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CXCL12 secreted from glioma stem cells regulates their proliferation

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Abstract

Emerging evidence suggests that the chemokine CXCL12 and its receptor CXCR4, which are expressed by glioma stem cells (GSCs), play an important role in tumorigenesis. To provide evidence for establishing a new therapy targeting the CXCL12/CXCR4 pathway, we investigated whether CXCL12 secreted from GSCs contributed to their proliferation and promoted angiogenesis in murine GSCs. Angiogenetic functions and proliferation of GSCs with or without CXCL12 inhibitors were evaluated in an in vitro model using tube formation assays, RT-PCR, and proliferation, as well as in an in vivo syngenic model. In endothelial culture, the morphology and gene expression of GSCs changed from stem cell-like characteristics to endothelial cell-like features. CXCL12 expression increased in endothelial cell-like GSCs. CXCL12 blockage with siRNA or shRNA markedly inhibited cell proliferation in vitro. CXCL12 knockdown with shRNA also inhibited tumor growth in vivo. On the other hand, CXCL12/CXCR4 blockage affected neither tube formation in vitro nor angiogenesis in vivo. The CXCL12 secreted from GSCs (autocrine/paracrine CXCL12) regulates their proliferation, but probably not angiogenesis.

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Acknowledgments

This study was supported by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (No.: 30510169 to EI). The authors thank Hideyuki Saya for kindly providing the Tumor Sphere cell line (TS).

Conflict of interest

No conflict of interest exists.

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Authors and Affiliations

  1. Department of Neurosurgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan

    Youji Uemae, Eiichi Ishikawa, Satoru Osuka, Masahide Matsuda, Noriaki Sakamoto, Shingo Takano, Kei Nakai, Tetsuya Yamamoto & Akira Matsumura

  2. Division of Gene Regulation, Keio University School of Medicine, Tokyo, Japan

    Satoru Osuka

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  1. Youji Uemae
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  2. Eiichi Ishikawa
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Correspondence to Eiichi Ishikawa.

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Uemae, Y., Ishikawa, E., Osuka, S. et al. CXCL12 secreted from glioma stem cells regulates their proliferation. J Neurooncol 117, 43–51 (2014). https://doi.org/10.1007/s11060-014-1364-y

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  • DOI: https://doi.org/10.1007/s11060-014-1364-y

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