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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

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

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Autor(es):
Cardoso, Lais C. [1] ; Soares, Roseli da S. [1] ; Laurentino, Talita de S. [1] ; Lerario, Antonio M. [2] ; Marie, Suely K. N. [1] ; Oba-Shinjo, Sueli Mieko [1]
Número total de Autores: 6
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Lab Mol & Cellular Biol LIM 15, Fac Med FMUSP, Dept Neurol, BR-01246903 Sao Paulo - Brazil
[2] Univ Michigan, Dept Internal Med, Div Metab Endocrinol & Diabet, Ann Arbor, MI 48109 - USA
Número total de Afiliações: 2
Tipo de documento: Artigo Científico
Fonte: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 20, n. 5 MAR 1 2019.
Citações Web of Science: 0
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. (AU)

Processo FAPESP: 13/02162-8 - Patogênese molecular e caracterização de doenças monogênicas do desenvolvimento: um caminho para a medicina translacional
Beneficiário:Berenice Bilharinho de Mendonça
Linha de fomento: Auxílio à Pesquisa - Temático
Processo FAPESP: 15/03614-5 - Detalhamento funcional do papel de CD99 em astrocitomas
Beneficiário:Sueli Mieko Oba Shinjo
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 15/03995-9 - Detalhamento funcional do papel de CD99 em astrocitomas
Beneficiário:Laís Cavalca Cardoso
Linha de fomento: Bolsas no Brasil - Doutorado
Processo FAPESP: 04/12133-6 - Procura de marcadores moleculares relacionados ao diagnóstico e prognóstico de tumores do sistema nervoso central
Beneficiário:Suely Kazue Nagahashi Marie
Linha de fomento: Auxílio à Pesquisa - Temático
Processo FAPESP: 01/12898-4 - Genoma clínico
Beneficiário:Suely Kazue Nagahashi Marie
Linha de fomento: Auxílio à Pesquisa - Programa GENOMA