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Mesenchymal Stem Cells Isolated From Human Gliomas Increase Proliferation and Maintain Stemness of Glioma Stem Cells Through the IL-6/gp130/STAT3 Pathway

 Anwar Hossain  ;  Joy Gumin  ;  Feng Gao  ;  Javier Figueroa  ;  Naoki Shinojima  ;  Tatsuya Takezaki  ;  Waldemar Priebe  ;  Diana Villarreal  ;  Seok-Gu Kang  ;  Celine Joyce  ;  Erik Sulman  ;  Qianghu Wang  ;  Frank C. Marini  ;  Michael Andreeff  ;  Howard Colman  ;  Frederick F. Lang 
 STEM CELLS, Vol.33(8) : 2400-2415, 2015 
Journal Title
Issue Date
Cell Proliferation* ; Cytokine Receptor gp130/metabolism* ; Female ; Glioma/metabolism* ; Glioma/pathology ; Humans ; Interleukin-6/metabolism* ; Male ; Mesenchymal Stromal Cells/metabolism* ; Mesenchymal Stromal Cells/pathology ; STAT3 Transcription Factor/metabolism* ; Signal Transduction*
Glioma stem cells ; Mesenchymal stem cells ; Glioblastoma ; Brain Tumor ; Interleukin-6 ; STAT3
Although mesenchymal stem cells (MSCs) have been implicated as stromal components of several cancers, their ultimate contribution to tumorigenesis and their potential to drive cancer stem cells, particularly in the unique microenvironment of human brain tumors, remain largely undefined. Consequently, using established criteria, we isolated glioma-associated-human MSCs (GA-hMSCs) from fresh human glioma surgical specimens for the first time. We show that these GA-hMSCs are nontumorigenic stromal cells that are phenotypically similar to prototypical bone marrow-MSCs. Low-passage genomic sequencing analyses comparing GA-hMSCs with matched tumor-initiating glioma stem cells (GSCs) suggest that most GA-hMSCs (60%) are normal cells recruited to the tumor (group 1 GA-hMSCs), although, rarely (10%), GA-hMSCs may differentiate directly from GSCs (group 2 GA-hMSCs) or display genetic patterns intermediate between these groups (group 3 GA-hMSCs). Importantly, GA-hMSCs increase proliferation and self-renewal of GSCs in vitro and enhance GSC tumorigenicity and mesenchymal features in vivo, confirming their functional significance within the GSC niche. These effects are mediated by GA-hMSC-secreted interleukin-6, which activates STAT3 in GSCs. Our results establish GA-hMSCs as a potentially new stromal component of gliomas that drives the aggressiveness of GSCs, and point to GA-hMSCs as a novel therapeutic target within gliomas.
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1. College of Medicine (의과대학) > Dept. of Neurosurgery (신경외과학교실) > 1. Journal Papers
Yonsei Authors
Kang, Seok Gu(강석구) ORCID logo https://orcid.org/0000-0001-5676-2037
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