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Balça-Silva J, Matias D, Dubois LG, et al. The Expression of Connexins and SOX2 Reflects the Plasticity of Glioma Stem-Like Cells. Transl Oncol. 2017;10(4):555-569doi: 10.1016/j.tranon.2017.04.005.
Balça-Silva, J., Matias, D., Dubois, L. G., Carneiro, B., do Carmo, A., Girão, H., Ferreira, F., Ferrer, V. P., Chimelli, L., Filho, P. N., Tão, H., Rebelo, O., Barbosa, M., Sarmento-Ribeiro, A. B., Lopes, M. C., & Moura-Neto, V. (2017). The Expression of Connexins and SOX2 Reflects the Plasticity of Glioma Stem-Like Cells. Translational oncology, 10(4), 555-569. https://doi.org/10.1016/j.tranon.2017.04.005
Balça-Silva, Joana, et al. "The Expression of Connexins and SOX2 Reflects the Plasticity of Glioma Stem-Like Cells." Translational oncology vol. 10,4 (2017): 555-569. doi: https://doi.org/10.1016/j.tranon.2017.04.005
Balça-Silva J, Matias D, Dubois LG, Carneiro B, do Carmo A, Girão H, Ferreira F, Ferrer VP, Chimelli L, Filho PN, Tão H, Rebelo O, Barbosa M, Sarmento-Ribeiro AB, Lopes MC, Moura-Neto V. The Expression of Connexins and SOX2 Reflects the Plasticity of Glioma Stem-Like Cells. Transl Oncol. 2017 Aug;10(4):555-569. doi: 10.1016/j.tranon.2017.04.005. Epub 2017 Jun 24. PMID: 28654819; PMCID: PMC5487246.
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Transl Oncol. 2017 Aug;10(4):555-569. doi: 10.1016/j.tranon.2017.04.005. Epub 2017 Jun 24.

The Expression of Connexins and SOX2 Reflects the Plasticity of Glioma Stem-Like Cells.

Translational oncology

Joana Balça-Silva, Diana Matias, Luiz Gustavo Dubois, Brenno Carneiro, Anália do Carmo, Henrique Girão, Fernanda Ferreira, Valeria Pereira Ferrer, Leila Chimelli, Paulo Niemeyer Filho, Hermínio Tão, Olinda Rebelo, Marcos Barbosa, Ana Bela Sarmento-Ribeiro, Maria Celeste Lopes, Vivaldo Moura-Neto

Affiliations

  1. Center for Neuroscience and Cell Biology and Institute for Biomedical Imaging and Life Sciences (CNC.IBILI), Coimbra, Portugal; Faculty of Medicine, University of Coimbra (FMUC), Coimbra, Portugal; Instituto Estadual do Cérebro Paulo Niemeyer (IECPN)-Secretaria de Estado de Saúde, Rio de Janeiro, Brazil. Electronic address: [email protected].
  2. Instituto Estadual do Cérebro Paulo Niemeyer (IECPN)-Secretaria de Estado de Saúde, Rio de Janeiro, Brazil; Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. Electronic address: [email protected].
  3. Instituto Estadual do Cérebro Paulo Niemeyer (IECPN)-Secretaria de Estado de Saúde, Rio de Janeiro, Brazil. Electronic address: [email protected].
  4. Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. Electronic address: [email protected].
  5. Center for Neuroscience and Cell Biology and Institute for Biomedical Imaging and Life Sciences (CNC.IBILI), Coimbra, Portugal; Clinical Pathology Department, Coimbra Hospital and Universitary Center (CHUC), Coimbra, Portugal. Electronic address: [email protected].
  6. Center for Neuroscience and Cell Biology and Institute for Biomedical Imaging and Life Sciences (CNC.IBILI), Coimbra, Portugal; Faculty of Medicine, University of Coimbra (FMUC), Coimbra, Portugal. Electronic address: [email protected].
  7. Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. Electronic address: [email protected].
  8. Instituto Estadual do Cérebro Paulo Niemeyer (IECPN)-Secretaria de Estado de Saúde, Rio de Janeiro, Brazil. Electronic address: [email protected].
  9. Instituto Estadual do Cérebro Paulo Niemeyer (IECPN)-Secretaria de Estado de Saúde, Rio de Janeiro, Brazil. Electronic address: [email protected].
  10. Instituto Estadual do Cérebro Paulo Niemeyer (IECPN)-Secretaria de Estado de Saúde, Rio de Janeiro, Brazil. Electronic address: [email protected].
  11. Neurosurgery Service, Centro Hospitalar Universitário de Coimbra (CHUC), Coimbra, Portugal. Electronic address: [email protected].
  12. Neuropathology Laboratory, Neurology Service, Centro Hospitalar Universitário de Coimbra (CHUC), Coimbra, Portugal. Electronic address: [email protected].
  13. Faculty of Medicine, University of Coimbra (FMUC), Coimbra, Portugal; Neurosurgery Service, Centro Hospitalar Universitário de Coimbra (CHUC), Coimbra, Portugal. Electronic address: [email protected].
  14. Center for Neuroscience and Cell Biology and Institute for Biomedical Imaging and Life Sciences (CNC.IBILI), Coimbra, Portugal; Faculty of Medicine, University of Coimbra (FMUC), Coimbra, Portugal; Laboratory of Oncobiology and Hematology and CIMAGO, Faculty of Medicine, University of Coimbra (FMUC), Coimbra, Portugal; Hematology Department, Centro Hospitalar Universitário de Coimbra (CHUC), Coimbra, Portugal. Electronic address: [email protected].
  15. Center for Neuroscience and Cell Biology and Institute for Biomedical Imaging and Life Sciences (CNC.IBILI), Coimbra, Portugal; Faculty of Pharmacy, University of Coimbra (FFUC), Coimbra, Portugal. Electronic address: [email protected].
  16. Instituto Estadual do Cérebro Paulo Niemeyer (IECPN)-Secretaria de Estado de Saúde, Rio de Janeiro, Brazil. Electronic address: [email protected].

PMID: 28654819 PMCID: PMC5487246 DOI: 10.1016/j.tranon.2017.04.005

Abstract

Glioblastoma (GBM) is the most malignant primary brain tumor, with an average survival rate of 15 months. GBM is highly refractory to therapy, and such unresponsiveness is due, primarily, but not exclusively, to the glioma stem-like cells (GSCs). This subpopulation express stem-like cell markers and is responsible for the heterogeneity of GBM, generating multiple differentiated cell phenotypes. However, how GBMs maintain the balance between stem and non-stem populations is still poorly understood. We investigated the GBM ability to interconvert between stem and non-stem states through the evaluation of the expression of specific stem cell markers as well as cell communication proteins. We evaluated the molecular and phenotypic characteristics of GSCs derived from differentiated GBM cell lines by comparing their stem-like cell properties and expression of connexins. We showed that non-GSCs as well as GSCs can undergo successive cycles of gain and loss of stem properties, demonstrating a bidirectional cellular plasticity model that is accompanied by changes on connexins expression. Our findings indicate that the interconversion between non-GSCs and GSCs can be modulated by extracellular factors culminating on differential expression of stem-like cell markers and cell-cell communication proteins. Ultimately, we observed that stem markers are mostly expressed on GBMs rather than on low-grade astrocytomas, suggesting that the presence of GSCs is a feature of high-grade gliomas. Together, our data demonstrate the utmost importance of the understanding of stem cell plasticity properties in a way to a step closer to new strategic approaches to potentially eliminate GSCs and, hopefully, prevent tumor recurrence.

Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

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