CD99 Expression in Glioblastoma Molecular Subtypes and Role in Migration and Invasion

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art_CARDOSO_CD99_Expression_in_Glioblastoma_Molecular_Subtypes_and_Role_2019.PDF (2.21 MB)
Citações na Scopus
18
Tipo de produção
article
Data de publicação
2019
Editora
MDPI
DOI
Indexadores
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Autores
SOARES, Roseli da S.
LERARIO, Antonio M.
Autor de Grupo de pesquisa
Editores
Coordenadores
Organizadores
Citação
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v.20, n.5, article ID 1137, 17p, 2019
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Glioblastoma (GBM) is the most aggressive type of brain tumor, with an overall survival of 17 months under the current standard of care therapy. CD99, an over-expressed transmembrane protein in several malignancies, has been considered a potential target for immunotherapy. To further understand this potentiality, we analyzed the differential expression of its two isoforms in human astrocytoma specimens, and the CD99 involved signaling pathways in glioma model U87MG cell line. CD99 was also analyzed in GBM molecular subtypes. Whole transcriptomes by RNA-Seq of CD99-siRNA, and functional in vitro assays in CD99-shRNA, that are found in U87MG cells, were performed. Astrocytoma of different malignant grades and U87MG cells only expressed CD99 isoform 1, which was higher in mesenchymal and classical than in proneural GBM subtypes. Genes related to actin dynamics, predominantly to focal adhesion, and lamellipodia/filopodia formation were down-regulated in the transcriptome analysis, when CD99 was silenced. A decrease in tumor cell migration/invasion, and dysfunction of focal adhesion, were observed in functional assays. In addition, a striking morphological change was detected in CD99-silenced U87MG cells, further corroborating CD99 involvement in actin cytoskeleton rearrangement. Inhibiting the overexpressed CD99 may improve resectability and decrease the recurrence rate of GBM by decreasing tumor cells migration and invasion.
Palavras-chave
glioblastoma, CD99, migration, cytoskeleton, transcriptome
URI
https://observatorio.fm.usp.br/handle/OPI/31732
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Coleções
Artigos e Materiais de Revistas Científicas - FM/MNE
Artigos e Materiais de Revistas Científicas - LIM/15
Artigos e Materiais de Revistas Científicas - ODS/03