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Brain Res. 2013 Nov 13;1538:151-8. doi: 10.1016/j.brainres.2013.02.025. Epub 2013 Mar 5.

ADAM17 promotes U87 glioblastoma stem cell migration and invasion.

Author information

  • 1Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, Guangdong Province, China; Department of Neurosurgery, the Second Affiliated Hospital, Fujian Medical University, Quanzhou 362000, Fujian Province, China.

Erratum in

  • Brain Res. 2013 Nov 13;1538:182.

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.

KEYWORDS:

ADAM17; Cancer stem cell; Glioblastoma; Invasion; Migration

PMID:
23470260
DOI:
10.1016/j.brainres.2013.02.025
[PubMed - indexed for MEDLINE]
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