title: Mesenchymal Stem Cells Isolated From Human Gliomas Increase Proliferation and Maintain Stemness of Glioma Stem Cells Through the IL-6/gp130/STAT3 Pathway.
abstract: 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.
authors.affiliation: Department of Neurosurgery.|Brain Tumor Center, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Anwar
authors.initials: A
authors.lastname: Hossain
authors.affiliation: Department of Neurosurgery.|Brain Tumor Center, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Joy
authors.initials: J
authors.lastname: Gumin
authors.affiliation: Department of Neurosurgery.|Brain Tumor Center, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.affiliation: Department of Neurosurgery.|Brain Tumor Center, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Javier
authors.initials: J
authors.lastname: Figueroa
authors.affiliation: Department of Neurosurgery.|Brain Tumor Center, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Naoki
authors.initials: N
authors.lastname: Shinojima
authors.affiliation: Department of Neurosurgery.|Brain Tumor Center, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Takezaki
authors.affiliation: Department of Experimental Therapeutics.|Brain Tumor Center, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Waldemar
authors.initials: W
authors.lastname: Priebe
authors.affiliation: Department of Neurosurgery.|Brain Tumor Center, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Diana
authors.initials: D
authors.lastname: Villarreal
authors.affiliation: Department of Neurosurgery.|Brain Tumor Center, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Seok-Gu
authors.initials: SG
authors.lastname: Kang
authors.affiliation: Department of Neurosurgery.|Brain Tumor Center, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Celine
authors.initials: C
authors.lastname: Joyce
authors.affiliation: Department of Radiation Oncology.|Brain Tumor Center, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Erik
authors.initials: E
authors.lastname: Sulman
authors.affiliation: Department of Bioinformatics and Computational Biology.|Brain Tumor Center, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Qianghu
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
authors.forename: Frank C
authors.initials: FC
authors.lastname: Marini
authors.affiliation: Department of Leukemia.
authors.forename: Michael
authors.initials: M
authors.lastname: Andreeff
authors.affiliation: Department of Neuro-Oncology, University of Utah Health Science Center, Salt Lake City, Utah, USA.
authors.forename: Howard
authors.initials: H
authors.lastname: Colman
authors.affiliation: Department of Neurosurgery.|Brain Tumor Center, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Frederick F
authors.initials: FF
authors.lastname: Lang
mesh_terms: D049109:Cell Proliferation; D050822:Cytokine Receptor gp130 / Q000378:metabolism*; D005260:Female; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000473:pathology; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D050822:Cytokine Receptor gp130
keywords: Brain tumor; Glioblastoma; Glioma stem cells; Interleukin-6; Mesenchymal stem cells; STAT3