Establishment of primary cell culture and an intracranial xenograft model of pediatric ependymoma: a prospect for therapy development and understanding of tumor biology
Pavon, Lorena Favaro; Sibov, Tatiana Tais; Toledo, Silvia Regina Caminada de; Oliveira, Daniela Mara de; Cabral, Francisco Romero; Souza, Jean Gabriel de ; Boufleur, Pâmela ; Marti, Luciana C.; Malheiros, Jackeline Moraes; Cruz, Edgar Ferreira da; Paiva, Fernando F.; Malheiros, Suzana M. F.; Paiva Neto, Manoel A. de; Tannús, Alberto; Oliveira, Sergio Mascarenhas de; Silva, Nasjla Saba; Cappellano, Andrea Maria; Petrilli, Antonio Sérgio; Chudzinski-Tavassi, Ana Marisa ; Cavalheiro, Sérgio
Background: Ependymoma (EPN), the third most common pediatric brain tumor, is a central nervous system (CNS) malignancy originating from the walls of the ventricular system. Surgical resection followed by radiation therapy has been the primary treatment for most pediatric intracranial EPNs. Despite numerous studies into the prognostic value of histological classification, the extent of surgical resection and adjuvant radiotherapy, there have been relatively few studies into the molecular and cellular biology of EPNs. Results: We elucidated the ultrastructure of the cultured EPN cells and characterized their profile of immunophenotypic pluripotency markers (CD133, CD90, SSEA-3, CXCR4). We established an experimental EPN model by the intracerebroventricular infusion of EPN cells labeled with multimodal iron oxide nanoparticles (MION), thereby generating a tumor and providing a clinically relevant animal model. MRI analysis was shown to be a valuable tool when combined with effective MION labeling techniques to accompany EPN growth. Conclusions: We demonstrated that GFAP/CD133+CD90+/CD44+ EPN cells maintained key histopathological and growth characteristics of the original patient tumor. The characterization of EPN cells and the experimental model could facilitate biological studies and preclinical drug screening for pediatric EPNs. Methods: In this work, we established notoriously challenging primary cell culture of anaplastic EPNs (WHO grade III) localized in the posterior fossa (PF), using EPNs obtained from 1 to 10-year-old patients (n = 07), and then characterized their immunophenotype and ultrastructure to finally develop a xenograft model.
primary culture EPN cells; pluripotency markers; animal model; MRI; preclinical studies
Pavon LF, Sibov TT, Toledo SRC, Oliveira DM, Cabral FR, Souza JG, et al. Establishment of primary cell culture and an intracranial xenograft model of pediatric ependymoma: a prospect for therapy development and understanding of tumor biology. Oncotarget. 2018;9(31):21731-43. doi:10.18632/oncotarget.24932.
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