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

• Published in: International journal of molecular sciences 2019-03, Vol.20 (5), p.1137
• Main Authors: Cardoso, Lais C, Soares, Roseli da S, Laurentino, Talita de S, Lerario, Antonio M, Marie, Suely K N, Oba-Shinjo, Sueli Mieko
• Format: Article
• Language: English
• Subjects: 12E7 Antigen - genetics; 12E7 Antigen - metabolism; Actin; Amino acids; Antigens; Apoptosis; Bone cancer; Brain cancer; Brain Neoplasms - genetics; Brain Neoplasms - metabolism; Breast cancer; CD99 antigen; Cell activation; Cell adhesion; Cell adhesion & migration; Cell differentiation; Cell Line, Tumor; Cell Movement; Cell proliferation; Cytology; Differentiation (biology); Extracellular matrix; Focal Adhesion Kinase 1 - genetics; Gene expression; Gene Expression Profiling - methods; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; Genes, src - genetics; Glioblastoma; Glioblastoma - genetics; Glioblastoma - metabolism; Humans; Immunotherapy; Inflammation; Leukemia; LFA-1 antigen; Ligands; Lymphocytes; Lymphocytes T; Lymphoma; Medical prognosis; Membrane proteins; Membranes; Microfilaments; Monoclonal antibodies; Neoplasm Invasiveness; Protein Isoforms - genetics; Protein Isoforms - metabolism; Proteins; RNA, Small Interfering - pharmacology; Sequence Analysis, RNA; Signal transduction; Tumor cells; Tumors; Up-Regulation
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20051137

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 -siRNA, and functional in vitro assays in -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 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 -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.