title: Microtubule-severing ATPase spastin in glioblastoma: increased expression in human glioblastoma cell lines and inverse roles in cell motility and proliferation.
abstract: We studied the expression and distribution of the microtubule-severing enzyme spastin in 3 human glioblastoma cell lines (U87MG, U138MG, and T98G) and in clinical tissue samples representative of all grades of diffuse astrocytic gliomas (n = 45). In adult human brains, spastin was distributed predominantly in neuronsand neuropil puncta and, to a lesser extent, in glia. Compared with normal mature brain tissues, spastin expression and cellular distribution were increased in neoplastic glial phenotypes, especiallyin glioblastoma (p < 0.05 vs low-grade diffuse astrocytomas). Overlapping punctate and diffuse patterns of localization wereidentified in tumor cells in tissues and in interphase and mitotic cells ofglioblastoma cell lines. There was enrichment of spastin in the leading edges of cells in T98G glioblastoma cell cultures and in neoplastic cell populations in tumor specimens. Real-time polymerase chain reaction and immunoblotting experiments revealed greater levels of spastin messenger RNA and protein expression in theglioblastoma cell lines versus normal human astrocytes. Functional experiments indicated that spastin depletion resulted in reduced cell motility and higher cell proliferation of T98G cells. Toour knowledge, this is the first report of spastin involvement incellmotility. Collectively, our results indicate that spastinexpression in glioblastomas might be linked to tumor cell motility, migration, and invasion.
authors.affiliation: Department of the Biology of Cytoskeleton, Institute of Molecular Genetics, Czech Republic.
authors.forename: Eduarda
authors.initials: E
authors.lastname: Dráberová
authors.forename: Stanislav
authors.initials: S
authors.lastname: Vinopal
authors.forename: Gerardo
authors.initials: G
authors.lastname: Morfini
authors.forename: Pei S
authors.initials: PS
authors.lastname: Liu
authors.forename: Vladimíra
authors.initials: V
authors.lastname: Sládková
authors.forename: Tetyana
authors.initials: T
authors.lastname: Sulimenko
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Burns
authors.forename: Joanna
authors.initials: J
authors.lastname: Solowska
authors.forename: Kandan
authors.initials: K
authors.lastname: Kulandaivel
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: de Chadarévian
authors.forename: Agustin
authors.initials: A
authors.lastname: Legido
authors.forename: Sverre J
authors.initials: SJ
authors.lastname: Mörk
authors.forename: Jiří
authors.initials: J
authors.lastname: Janáček
authors.forename: Peter W
authors.initials: PW
authors.lastname: Baas
authors.forename: Pavel
authors.initials: P
authors.lastname: Dráber
authors.forename: Christos D
authors.initials: CD
authors.lastname: Katsetos
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D000367:Age Factors; D001921:Brain / Q000201:enzymology / Q000473:pathology; D001932:Brain Neoplasms / Q000201:enzymology* / Q000473:pathology; D002452:Cell Count / Q000379:methods; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation; D002648:Child; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D005909:Glioblastoma / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D007223:Infant; D008297:Male; D008870:Microtubules; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D000074181:Spastin; D055815:Young Adult
chemical_list: D012333:RNA, Messenger; D000251:Adenosine Triphosphatases; D000074181:Spastin; C400283:SPAST protein, human