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CD99 is upregulated in placenta and astrocytomas with a differential subcellular distribution according to the malignancy stage

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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.

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Acknowledgments

We are very thankful for all the neurosurgeons of the Division of Neurosurgery of the Department of Neurology at Hospital das Clínicas of School of Medicine, University of São Paulo for the therapeutic and follow-up procedures of all patients included in this study. We particularly acknowledge Thais F. Galatro for the valuable immunohistochemistry reactions. This work was supported by grants #04/12133-6 and #06/56989-7, São Paulo Research Foundation (FAPESP), the Ludwig Institute for Cancer Research, National Council for Scientific and Technological Development (CNPq), and Fundação Faculdade de Medicina (FFM).

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical standards

The experiments comply with the current laws of Brazil.

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Authors and Affiliations

  1. Laboratory of Molecular and Cellular Biology, Department of Neurology, Faculdade de Medicina da, Universidade de São Paulo, São Paulo, SP, 01246-903, Brazil

    Úrsula Urias, Suely K. N. Marie, Miyuki Uno, Roseli da Silva, Mariá M. Evagelinellis & Sueli M. Oba-Shinjo

  2. Ludwig Institute for Cancer Research, New York Branch at Memorial Sloan-Kettering Cancer Center, New York, NY, 10065, USA

    Otavia L. Caballero

  3. Ludwig Institute for Cancer Research, University of Lausanne, 1015, Lausanne, Switzerland

    Brian J. Stevenson

  4. Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, 14049-900, Brazil

    Wilson A. Silva Jr.

  5. Center for Integrative Systems Biology (CISBi-NAP), University of São Paulo, Ribeirão Preto, SP, 14049-900, Brazil

    Wilson A. Silva Jr.

  6. Ludwig Institute for Cancer Research, 666 Third Avenue, New York, NY, 10017, USA

    Andrew J. Simpson

  7. Center for Studies of Cellular and Molecular Therapy (NETCEM), University of São Paulo, São Paulo, Brazil

    Suely K. N. Marie

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  1. Úrsula Urias
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  2. Suely K. N. Marie
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  4. Roseli da Silva
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  10. Sueli M. Oba-Shinjo
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Correspondence to Sueli M. Oba-Shinjo.

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Urias, Ú., Marie, S.K.N., Uno, M. et al. CD99 is upregulated in placenta and astrocytomas with a differential subcellular distribution according to the malignancy stage. J Neurooncol 119, 59–70 (2014). https://doi.org/10.1007/s11060-014-1462-x

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