title: Wnt activation affects proliferation, invasiveness and radiosensitivity in medulloblastoma.
abstract: Medulloblastomas (MBs) associated with the Wnt activation represent a subgroup with a favorable prognosis, but it remains unclear whether Wnt activation confers a less aggressive phenotype and/or enhances radiosensitivity. To investigate this issue, we evaluated the biological behavior of an MB cell line, UW228-1, stably transfected with human β-catenin cDNA encoding a nondegradable form of β-catenin (UW-B) in standard culture conditions and after radiation treatment. We evaluated the expression, transcriptional activity, and localization of β-catenin in the stably transfected cells using immunofluorescence and WB. We performed morphological analysis using light and electron microscopy. We then analyzed changes in the invasiveness, growth, and mortality in standard culture conditions and after radiation. We demonstrated that (A) Wnt activation inhibited 97 % of the invasion capability of the cells, (B) the growth of the UW-B cells was statistically significantly lower than that of all the other control cells (p < 0.01), (C) the mortality of irradiated UW-B cells was statistically significantly higher than that of the controls and their nonirradiated counterparts (p < 0.05), and (D) morphological features of neuronal differentiation were observed in the Wnt-activated cells. In tissue samples, the Ki-67 labeling index (LI) was lower in β-catenin-positive samples compared to non-β-catenin positive ones. The Ki-67 LI median (LI = 40) of the nuclear β-catenin-positive tumor samples was lower than that of non-nuclear β-catenin-positive samples (LI = 50), but the difference was not statistically significant. Overall, our data suggest that activation of the Wnt pathway reduces the proliferation and invasion of MBs and increases the tumor's radiosensitivity.
authors.affiliation: Department of Biomedical and Neuromotor Sciences, "Alma Mater Studiorum" University of Bologna, Via Massarenti 9, 40138, Bologna, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Salaroli
authors.forename: Alice
authors.initials: A
authors.lastname: Ronchi
authors.forename: Francesca Romana
authors.initials: FR
authors.lastname: Buttarelli
authors.forename: Filippo
authors.initials: F
authors.lastname: Cortesi
authors.forename: Valeria
authors.initials: V
authors.lastname: Marchese
authors.forename: Elena
authors.initials: E
authors.lastname: Della Bella
authors.forename: Cristiano
authors.initials: C
authors.lastname: Renna
authors.forename: Caterina
authors.initials: C
authors.lastname: Baldi
authors.forename: Felice
authors.initials: F
authors.lastname: Giangaspero
authors.forename: Giovanna
authors.initials: G
authors.lastname: Cenacchi
mesh_terms: D000293:Adolescent; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D002648:Child; D002675:Child, Preschool; D005455:Fluorescent Antibody Technique; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D019394:Ki-67 Antigen / Q000378:metabolism; D008527:Medulloblastoma / Q000473:pathology / Q000503:physiopathology* / Q000532:radiotherapy*; D046529:Microscopy, Electron, Transmission; D009361:Neoplasm Invasiveness / Q000503:physiopathology; D055495:Neurogenesis / Q000502:physiology; D011836:Radiation Tolerance / Q000502:physiology*; D014162:Transfection; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: C495270:CTNNB1 protein, human; D019394:Ki-67 Antigen; D051153:Wnt Proteins; D051176:beta Catenin