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Establishment of primary cell culture and an intracranial xenograft model of pediatric ependymoma: a prospect for therapy development and understanding of tumor biology

2018; Impact Journals LLC; Volume: 9; Issue: 31 Linguagem: Inglês

10.18632/oncotarget.24932

1949-2553

Lorena Favaro Pavon, Tatiana Taís Sibov, Sílvia Regina Caminada de Toledo, Daniela Mara de Oliveira, Francisco Romero Cabral, Jean Gabriel de Souza, Pamela Boufleur, Luciana Cavalheiro Marti, Jackeline Moraes Malheiros, Edgar Ferreira da Cruz, Fernando Fernandes Paiva, Suzana Mária Fleury Malheiros, Manoel Antônio de Paiva Neto, Alberto Tannús, Sérgio Mascarenhas de Oliveira, Nasjla Saba Silva, Andréa Cappellano, Antônio Sérgio Petrilli, Ana Marisa Chudzinski‐Tavassi, Sérgio Cavalheiro,

Neuroblastoma Research and Treatments

// Lorena Favaro Pavon 1 , Tatiana Tais Sibov 1 , Silvia Regina Caminada de Toledo 2 , Daniela Mara de Oliveira 3 , Francisco Romero Cabral 4 , Jean Gabriel de Souza 5 , Pamela Boufleur 5 , Luciana C. Marti 4, 6 , Jackeline Moraes Malheiros 7 , Edgar Ferreira da Cruz 8 , Fernando F. Paiva 9 , Suzana M.F. Malheiros 1, 4 , Manoel A. de Paiva Neto 1 , Alberto Tannús 9 , Sérgio Mascarenhas de Oliveira 9 , Nasjla Saba Silva 2 , Andrea Maria Cappellano 2 , Antonio Sérgio Petrilli 2 , Ana Marisa Chudzinski-Tavassi 5 and Sérgio Cavalheiro 1, 2 1 Department of Neurology and Neurosurgery, Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil 2 Pediatric Oncology Institute, Grupo de Apoio ao Adolescente e à Criança com Câncer (GRAACC), Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil 3 Department of Genetics and Morphology, Universidade de Brasília, Brasília, Brazil 4 Hospital Israelita Albert Einstein (HIAE), São Paulo, Brazil 5 Biochemistry and Biophysics Laboratory, Butantan Institute, São Paulo, Brazil 6 Allergy and Immunopathology Graduate Program, Faculdade de Medicina, Universidade de São Paulo (USP), São Paulo, Brazil 7 Department of Physiology, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil 8 Discipline of Nephrology, Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil 9 São Carlos Institute of Physics, Universidade de São Paulo (USP), São Paulo, Brazil Correspondence to: Lorena Favaro Pavon, email: l.pavon@unifesp.br , lorenap20111@hotmail.com Keywords: primary culture EPN cells; pluripotency markers; animal model; MRI; preclinical studies Received: November 15, 2017 Accepted: March 06, 2018 Published: April 24, 2018 ABSTRACT 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.