title: CD99 is upregulated in placenta and astrocytomas with a differential subcellular distribution according to the malignancy stage.
abstract: In the present study, we searched for genes highly expressed in placenta and that could contribute to the establishment and maintenance of a malignant phenotype in different types of tumours, and in astrocytomas in particular. We employed a strategy based on the integration of in silico data from previously generated massively parallel signature sequencing and public serial analysis of gene expression databases. Among 12 selected genes, CD99 exhibited the highest relative mRNA expression in GBM compared to non-neoplastic brain tissues. In a larger cohort of astrocytic tumours, we further demonstrated increased CD99 expression in all malignant grades, with GBMs showing the highest values. These findings were confirmed at the protein level by Western blotting and immunohistochemistry. Additionally, we demonstrated the CD99 localisation profile in astrocytic tumours. Interestingly, CD99 expression was confined to the cytoplasm or membrane in more malignant astrocytomas, in contrast to non-neoplastic brain tissue or non-infiltrative pilocytic astrocytoma, which showed no obvious staining in these structures. Comparison of three GBM cell lines revealed higher CD99 expression at the membrane and higher migratory capacity in the A172 and U87MG lines, but lower CD99 expression and no migratory ability in the T98 line. Knocking down CD99 expression by siRNA decreased significantly the migration of both cell lines. These integrated CD99 gene and protein expression results suggest that CD99 expression in astrocytomas of different malignant grades might contribute to the infiltrative ability and support the importance of CD99 as a potential target to reduce infiltrative astrocytoma capacity in migration and invasion.
authors.affiliation: Laboratory of Molecular and Cellular Biology, Department of Neurology, Faculdade de Medicina da, Universidade de São Paulo, São Paulo, SP, 01246-903, Brazil.
authors.forename: Ursula
authors.initials: U
authors.lastname: Úrias
authors.forename: Suely K N
authors.initials: SK
authors.lastname: Marie
authors.forename: Miyuki
authors.initials: M
authors.lastname: Uno
authors.forename: Roseli
authors.initials: R
authors.lastname: da Silva
authors.forename: Mariá M
authors.initials: MM
authors.lastname: Evagelinellis
authors.forename: Otavia L
authors.initials: OL
authors.lastname: Caballero
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Stevenson
authors.forename: Wilson A
authors.initials: WA
authors.lastname: Silva
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Simpson
authors.forename: Sueli M
authors.initials: SM
authors.lastname: Oba-Shinjo
mesh_terms: D000071443:12E7 Antigen; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D001254:Astrocytoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D060787:Neoplasm Grading; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D015854:Up-Regulation
chemical_list: D000071443:12E7 Antigen; D015703:Antigens, CD; C061828:CD99 protein, human; D015815:Cell Adhesion Molecules