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

Author(s)

Cardoso, Lais C. ; Soares, Roseli da S. ; Laurentino, Talita de S. ; Lerario, Antonio M. ; Marie, Suely K. N. ; Oba-Shinjo, Sueli Mieko

• Document type: Journal article
• Source: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 20, n. 5, p. 17-pg., 2019-03-01.

Abstract

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)

• FAPESP's process: 15/03614-5 - Functional detailing of CD99 role in astrocytomas
• Grantee: Sueli Mieko Oba Shinjo
• Support Opportunities: Regular Research Grants
• FAPESP's process: 13/02162-8 - Molecular pathogenesis and characterization of monogenic developmental diseases: a route to translational medicine
• Grantee: Berenice Bilharinho de Mendonça
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 15/03995-9 - Functional detailing of CD99 role in astrocytomas
• Grantee: Laís Cavalca Cardoso
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 04/12133-6 - Search for molecular markers related to the diagnosis and prognosis of tumors of the central nervous system
• Grantee: Suely Kazue Nagahashi Marie
• Support Opportunities: Research Projects - Thematic Grants