ADAM17 promotes U87 glioblastoma stem cell migration and invasion

Abstract Glioblastoma stem cells (GSCs) are thought to contribute to the diffuse invasiveness of malignant gliomas. Emerging evidence supports a role for a disintegrin and metalloproteinase 17 (ADAM17) in proteolytic ectodomain shedding of several EGFR-binding ligands, which subsequently activate PI...

Full description

Saved in:
Bibliographic Details
Published in:Brain research 2013-11, Vol.1538, p.151-158
Main Authors: Chen, Xiangrong, Chen, Lei, Chen, Junyan, Hu, Weipeng, Gao, Hongzhi, Xie, Baoyuan, Wang, Xin, Yin, Zhilin, Li, Shun, Wang, Xiangyu
Format: Article
Language:English
Subjects:
acetates
ADAM Proteins - metabolism
ADAM17
ADAM17 Protein
agonists
Antigens, CD - metabolism
Biological and medical sciences
brain
Cancer stem cell
Cell Line, Tumor
Cell Movement
chemokines
flow cytometry
fluorescent antibody technique
Glioblastoma
Glioblastoma - metabolism
Glioblastoma - pathology
Humans
Invasion
Medical sciences
Migration
Neoplasm Invasiveness
Neoplastic Stem Cells - physiology
Neurology
phosphorylation
proteolysis
Signal Transduction
stem cells
Tumors of the nervous system. Phacomatoses
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Abstract Glioblastoma stem cells (GSCs) are thought to contribute to the diffuse invasiveness of malignant gliomas. Emerging evidence supports a role for a disintegrin and metalloproteinase 17 (ADAM17) in proteolytic ectodomain shedding of several EGFR-binding ligands, which subsequently activate PI3K/AKT and MEK/ERK pathways through EGFR phosphorylation thus mediating glioma invasiveness. However, it is not clear if ADAM17 also plays important roles in promoting GSC invasion. In this study, we isolated CD133+ GSCs from the human glioblastoma cell line U87 using fluorescence-activated cell sorting and demonstrated their increased invasive potential compared with matched non-stem tumor cells. Furthermore, we showed that CD133+ GSCs expressed higher levels of ADAM17. Immunofluorescence staining revealed that high expression levels of ADAM17 at the invasive front were correlated with the presence of CD133+ GSCs in human glioblastoma specimens. Stimulation with the ADAM17 agonist chemokine phorbol myristate acetate increased migration and invasion of GSCs, which was counteracted by ADAM17 knockdown. In addition, ADAM17 also induced CD133+ GSC invasion via activation of the EGFR/PI3K/AKT signaling pathway. These findings suggest that ADAM17 is involved in U87 GSC invasive process and may provide a potential therapeutic target for glioma treatment.
ISSN:0006-8993
1872-6240
DOI:10.1016/j.brainres.2013.02.025