PMID- 26755664
OWN - NLM
STAT- MEDLINE
DCOM- 20170124
LR  - 20181113
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 7
IP  - 5
DP  - 2016 Feb 2
TI  - Preferential expression of functional IL-17R in glioma stem cells: potential role 
      in self-renewal.
PG  - 6121-35
LID - 10.18632/oncotarget.6847 [doi]
AB  - Gliomas are the most common primary brain tumor and one of the most lethal solid 
      tumors. Mechanistic studies into identification of novel biomarkers are needed to 
      develop new therapeutic strategies for this deadly disease. The objective for 
      this study was to explore the potential direct impact of IL-17-IL-17R interaction 
      in gliomas. Immunohistochemistry and flow cytometry analysis of 12 tumor samples 
      obtained from patients with high grade gliomas revealed that a considerable 
      population (2-19%) of cells in all malignant gliomas expressed IL-17RA, with 
      remarkable co-expression of the glioma stem cell (GSC) markers CD133, Nestin, and 
      Sox2. IL-17 enhanced the self-renewal of GSCs as determined by proliferation and 
      Matrigel(R) colony assays. IL-17 also induced cytokine/chemokine (IL-6, IL-8, 
      interferon-gamma-inducible protein [IP-10], and monocyte chemoattractant protein-1 
      [MCP-1]) secretion in GSCs, which were differentially blocked by antibodies 
      against IL-17R and IL-6R. Western blot analysis showed that IL-17 modulated the 
      activity of signal transducer and activator of transcription 3 (STAT3), nuclear 
      factor kappa-light-chain-enhancer of activated B cells (NF-kappaB), glycogen synthase 
      kinase-3beta (GSK-3beta) and beta-catenin in GSCs. While IL-17R-mediated secretion of IL-6 
      and IL-8 were significantly blocked by inhibitors of NF-kappaB and STAT3; NF-kappaB 
      inhibitor was more potent than STAT3 inhibitor in blocking IL-17-induced MCP-1 
      secretion. Overall, our results suggest that IL-17-IL-17R interaction in GSCs 
      induces an autocrine/paracrine cytokine feedback loop, which may provide an 
      important signaling component for maintenance/self-renewal of GSCs via 
      constitutive activation of both NF-kappaB and STAT3. The results also strongly 
      implicate IL-17R as an important functional biomarker for therapeutic targeting 
      of GSCs.
FAU - Parajuli, Prahlad
AU  - Parajuli P
AD  - Department of Neurosurgery, Wayne State University and Karmanos Cancer Institute, 
      Detroit, MI, USA.
FAU - Anand, Rohit
AU  - Anand R
AD  - Department of Neurosurgery, Wayne State University and Karmanos Cancer Institute, 
      Detroit, MI, USA.
FAU - Mandalaparty, Chandramouli
AU  - Mandalaparty C
AD  - Department of Neurosurgery, Wayne State University and Karmanos Cancer Institute, 
      Detroit, MI, USA.
FAU - Suryadevara, Raviteja
AU  - Suryadevara R
AD  - Department of Neurosurgery, Wayne State University and Karmanos Cancer Institute, 
      Detroit, MI, USA.
FAU - Sriranga, Preethi U
AU  - Sriranga PU
AD  - Department of Neurosurgery, Wayne State University and Karmanos Cancer Institute, 
      Detroit, MI, USA.
FAU - Michelhaugh, Sharon K
AU  - Michelhaugh SK
AD  - Department of Neurosurgery, Wayne State University and Karmanos Cancer Institute, 
      Detroit, MI, USA.
FAU - Cazacu, Simona
AU  - Cazacu S
AD  - Hermelin Brain Tumor Center, Henry Ford Hospital, Detroit, MI, USA.
FAU - Finniss, Susan
AU  - Finniss S
AD  - Hermelin Brain Tumor Center, Henry Ford Hospital, Detroit, MI, USA.
FAU - Thakur, Archana
AU  - Thakur A
AD  - Department of Oncology, Wayne State University and Karmanos Cancer Institute, 
      Detroit, MI, USA.
FAU - Lum, Lawrence G
AU  - Lum LG
AD  - Department of Oncology, Wayne State University and Karmanos Cancer Institute, 
      Detroit, MI, USA.
AD  - Departments of Internal Medicine, Immunology and Microbiology and Pediatrics, 
      Wayne State University, Detroit, MI, USA.
FAU - Schalk, Dana
AU  - Schalk D
AD  - Department of Oncology, Wayne State University and Karmanos Cancer Institute, 
      Detroit, MI, USA.
FAU - Brodie, Chaya
AU  - Brodie C
AD  - Hermelin Brain Tumor Center, Henry Ford Hospital, Detroit, MI, USA.
FAU - Mittal, Sandeep
AU  - Mittal S
AD  - Department of Neurosurgery, Wayne State University and Karmanos Cancer Institute, 
      Detroit, MI, USA.
AD  - Department of Oncology, Wayne State University and Karmanos Cancer Institute, 
      Detroit, MI, USA.
LA  - eng
GR  - R01 CA123451/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
RN  - 0 (IL17A protein, human)
RN  - 0 (Interleukin-17)
RN  - 0 (NF-kappa B)
SB  - IM
MH  - Aged
MH  - Cell Proliferation/physiology
MH  - Female
MH  - Glioma/genetics/*metabolism/pathology
MH  - Humans
MH  - Interleukin-17/*biosynthesis
MH  - Male
MH  - Middle Aged
MH  - NF-kappa B/metabolism
MH  - Signal Transduction
PMC - PMC4868744
OTO - NOTNLM
OT  - IL-17
OT  - IL-17R
OT  - IL-6
OT  - NF-kappaB
OT  - glioma stem cells (GSCs)
COIS- CONFLICTS OF INTEREST The authors declare that they have no conflicts of 
      interests or disclosures.
EDAT- 2016/01/13 06:00
MHDA- 2017/01/25 06:00
PMCR- 2016/02/02
CRDT- 2016/01/13 06:00
PHST- 2015/07/22 00:00 [received]
PHST- 2015/12/26 00:00 [accepted]
PHST- 2016/01/13 06:00 [entrez]
PHST- 2016/01/13 06:00 [pubmed]
PHST- 2017/01/25 06:00 [medline]
PHST- 2016/02/02 00:00 [pmc-release]
AID - 6847 [pii]
AID - 10.18632/oncotarget.6847 [doi]
PST - ppublish
SO  - Oncotarget. 2016 Feb 2;7(5):6121-35. doi: 10.18632/oncotarget.6847.