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Establishment of a novel human medulloblastoma cell line characterized by highly aggressive stem-like cells

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Abstract

Medulloblastoma is a highly aggressive brain tumor and one of the leading causes of morbidity and mortality related to childhood cancer. These tumors display differential ability to metastasize and respond to treatment, which reflects their high degree of heterogeneity at the genetic and molecular levels. Such heterogeneity of medulloblastoma brings an additional challenge to the understanding of its physiopathology and impacts the development of new therapeutic strategies. This translational effort has been the focus of most pre-clinical studies which invariably employ experimental models using human tumor cell lines. Nonetheless, compared to other cancers, relatively few cell lines of human medulloblastoma are available in central repositories, partly due to the rarity of these tumors and to the intrinsic difficulties in establishing continuous cell lines from pediatric brain tumors. Here, we report the establishment of a new human medulloblastoma cell line which, in comparison with the commonly used and well-established cell line Daoy, is characterized by enhanced proliferation and invasion capabilities, stem cell properties, increased chemoresistance, tumorigenicity in an orthotopic metastatic model, replication of original medulloblastoma behavior in vivo, strong chromosome structural instability and deregulation of genes involved in neural development. These features are advantageous for designing biologically relevant experimental models in clinically oriented studies, making this novel cell line, named USP-13-Med, instrumental for the study of medulloblastoma biology and treatment.

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Acknowledgments

The authors thank Dr. Carla Rosenberg for supervising the CNA analysis and for her helpful comments on the manuscript. This study was supported by funds from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), Grants FAPESP-CEPID (2013/08028-1), FAPESP (2010/52686-5); funds from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Grants CNPq (309206/2011-1; 444722/2014-9), INCT-CETGEN (573633/2008-8); and funds from Financiadora de Estudos e Projetos (FINEP), Grant FINEP-CTC (0108057900).

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Correspondence to Oswaldo Keith Okamoto.

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The authors disclose no potential conflicts of interest.

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Silva, P.B.G., Rodini, C.O., Kaid, C. et al. Establishment of a novel human medulloblastoma cell line characterized by highly aggressive stem-like cells. Cytotechnology 68, 1545–1560 (2016). https://doi.org/10.1007/s10616-015-9914-5

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  • DOI: https://doi.org/10.1007/s10616-015-9914-5

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