title: Targeting Netrin-1 in glioblastoma stem-like cells inhibits growth, invasion, and angiogenesis.
abstract: Glioblastoma (GBM) is an aggressive malignant brain tumor that still lacks effective therapy. Glioblastoma stem cells (GBM-SCs) were identified to contribute to aggressive phenotypes and poor clinical outcomes for GBM. Netrin-1, an axon guidance molecule, has been found in several tumors in adults. However, the role of Netrin-1 in GBM-SCs remains largely unknown. In this study, CD133-positive U251 GBM cells were used as a putative GBM-SC population to identify the functions of Netrin-1. Using lentiviral transduction, Netrin-1 miR RNAi vectors were transduced into CD133-positive U251 cells. We demonstrated that cell proliferation and survival were decreased following targeted deletion of Netrin-1. Cell invasion was dramatically diminished in Netrin-1 knockdown GBM-SCs. Moreover, Netrin-1 knockdown GBM-SCs exhibited less proangiogenic activity. In conclusion, Netrin-1 may represent a therapeutic target in glioblastoma.
authors.affiliation: Department of Clinical Microscopy, Faculty of Medical Technology, Mahidol University, Nakhon Pathom, Thailand.
authors.forename: Tanwarat
authors.initials: T
authors.lastname: Sanvoranart
authors.affiliation: Department of Clinical Microscopy, Faculty of Medical Technology, Mahidol University, Nakhon Pathom, Thailand.
authors.forename: Aungkura
authors.initials: A
authors.lastname: Supokawej
authors.affiliation: Division of Cell Biology, Department of Pre-clinical Sciences, Faculty of Medicine, Thammasat University, Pathumthani, Thailand.
authors.forename: Pakpoom
authors.initials: P
authors.lastname: Kheolamai
authors.affiliation: Division of Hematology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Wang Lang Road, Bangkoknoi, Bangkok, 10700, Thailand.|Siriraj Center of Excellence for Stem Cell Research, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Wang Lang Road, Bangkoknoi, Bangkok, 10700, Thailand.
authors.forename: Yaowalak
authors.initials: Y
authors.lastname: U-Pratya
authors.affiliation: Division of Neurology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Wang Lang Road, Bangkoknoi, Bangkok, 10700, Thailand.
authors.forename: Niphon
authors.initials: N
authors.lastname: Poungvarin
authors.affiliation: Division of Neurology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Wang Lang Road, Bangkoknoi, Bangkok, 10700, Thailand. drsith@gmail.com.|NANOTEC-Mahidol University Center of Excellence in Nanotechnology for Cancer Diagnosis and Treatment, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Wang Lang Road, Bangkoknoi, Bangkok, 10700, Thailand. drsith@gmail.com.
authors.forename: Sith
authors.initials: S
authors.lastname: Sathornsumetee
authors.affiliation: Division of Hematology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Wang Lang Road, Bangkoknoi, Bangkok, 10700, Thailand. surapolsi@gmail.com.|Siriraj Center of Excellence for Stem Cell Research, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Wang Lang Road, Bangkoknoi, Bangkok, 10700, Thailand. surapolsi@gmail.com.
authors.forename: Surapol
authors.initials: S
authors.lastname: Issaragrisil
mesh_terms: D000071916:AC133 Antigen / Q000378:metabolism; D000071437:Axon Guidance / Q000235:genetics; D001932:Brain Neoplasms / Q000235:genetics / Q000473:pathology; D049109:Cell Proliferation / Q000235:genetics*; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology*; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000235:genetics; D014411:Neoplastic Stem Cells / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000235:genetics*; D009414:Nerve Growth Factors / Q000235:genetics*; D000075388:Netrin-1; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D018874:Spheroids, Cellular; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D000071916:AC133 Antigen; C000617351:NTN1 protein, human; D009414:Nerve Growth Factors; C000606023:PROM1 protein, human; D034741:RNA, Small Interfering; D025521:Tumor Suppressor Proteins; D000075388:Netrin-1; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: Axon guidance; Glioblastoma; Glioblastoma stem-like cells; Netrin-1; Targeting