Wnt activation affects proliferation, invasiveness and radiosensitivity in medulloblastoma
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Wnt activation affects proliferation, invasiveness and radiosensitivity in medulloblastoma. / Salaroli, Roberta; Ronchi, Alice; Buttarelli, Francesca Romana; Cortesi, Filippo; Marchese, Valeria; Della Bella, Elena; Renna, Cristiano; Baldi, Caterina; Giangaspero, Felice; Cenacchi, Giovanna.
In: J NEURO-ONCOL, Vol. 121, No. 1, 01.2015, p. 119-27.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Wnt activation affects proliferation, invasiveness and radiosensitivity in medulloblastoma
AU - Salaroli, Roberta
AU - Ronchi, Alice
AU - Buttarelli, Francesca Romana
AU - Cortesi, Filippo
AU - Marchese, Valeria
AU - Della Bella, Elena
AU - Renna, Cristiano
AU - Baldi, Caterina
AU - Giangaspero, Felice
AU - Cenacchi, Giovanna
PY - 2015/1
Y1 - 2015/1
N2 - 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.
AB - 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.
KW - Adolescent
KW - Blotting, Western
KW - Cell Line, Tumor
KW - Cell Proliferation/drug effects
KW - Child
KW - Child, Preschool
KW - Fluorescent Antibody Technique
KW - Humans
KW - Infant
KW - Infant, Newborn
KW - Ki-67 Antigen/metabolism
KW - Medulloblastoma/pathology
KW - Microscopy, Electron, Transmission
KW - Neoplasm Invasiveness/physiopathology
KW - Neurogenesis/physiology
KW - Radiation Tolerance/physiology
KW - Transfection
KW - Wnt Proteins/metabolism
KW - beta Catenin/genetics
U2 - 10.1007/s11060-014-1621-0
DO - 10.1007/s11060-014-1621-0
M3 - SCORING: Journal article
C2 - 25261924
VL - 121
SP - 119
EP - 127
JO - J NEURO-ONCOL
JF - J NEURO-ONCOL
SN - 0167-594X
IS - 1
ER -
