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 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.

journal_name

Brain Res

journal_title

Brain research

authors

Chen X,Chen L,Chen J,Hu W,Gao H,Xie B,Wang X,Yin Z,Li S,Wang X

doi

10.1016/j.brainres.2013.02.025

subject

Has Abstract

pub_date

2013-11-13 00:00:00

pages

151-8

eissn

0006-8993

issn

1872-6240

pii

S0006-8993(13)00260-6

journal_volume

1538

pub_type

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