title: 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.
authors.affiliation: Department 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.
authors.forename: Xiangrong
authors.initials: X
authors.lastname: Chen
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.forename: Junyan
authors.initials: J
authors.lastname: Chen
authors.forename: Weipeng
authors.initials: W
authors.lastname: Hu
authors.forename: Hongzhi
authors.initials: H
authors.lastname: Gao
authors.forename: Baoyuan
authors.initials: B
authors.lastname: Xie
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Zhilin
authors.initials: Z
authors.lastname: Yin
authors.forename: Shun
authors.initials: S
authors.lastname: Li
authors.forename: Xiangyu
authors.initials: X
authors.lastname: Wang
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism*; D000072198:ADAM17 Protein; D015703:Antigens, CD / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D009361:Neoplasm Invasiveness; D014411:Neoplastic Stem Cells / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D015703:Antigens, CD; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human
keywords: ADAM17; Cancer stem cell; Glioblastoma; Invasion; Migration