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Wnt activation affects proliferation, invasiveness and radiosensitivity in medulloblastoma

  • Laboratory Investigation
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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.

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Acknowledgments

We thank Dr. Mike Bobola and Dr. Charles G. Eberhart for providing the human MB cell line UW228-1 and Dr. Hans Clevers for providing the plasmid construct.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Biomedical and Neuromotor Sciences, “Alma Mater Studiorum” University of Bologna, Via Massarenti 9, 40138, Bologna, Italy

    Roberta Salaroli, Alice Ronchi, Filippo Cortesi, Valeria Marchese, Elena Della Bella, Cristiano Renna & Giovanna Cenacchi

  2. Department of Radiology, Oncology and Anatomo-Pathology, Sapienza University of Rome, 00161, Rome, Italy

    Felice Giangaspero

  3. Neuromed IRCCS, 86077, Pozzilli, Italy

    Felice Giangaspero

  4. Department of Neurology and Psychiatry, Sapienza University of Rome, 00161, Rome, Italy

    Francesca Romana Buttarelli & Caterina Baldi

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  1. Roberta Salaroli
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Correspondence to Giovanna Cenacchi.

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Salaroli, R., Ronchi, A., Buttarelli, F.R. et al. Wnt activation affects proliferation, invasiveness and radiosensitivity in medulloblastoma. J Neurooncol 121, 119–127 (2015). https://doi.org/10.1007/s11060-014-1621-0

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  • DOI: https://doi.org/10.1007/s11060-014-1621-0

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