Differentiation of Human Glioblastoma Stem Cells as a Prospective Tool to Find New Biomarkers and Molecular Targets: A Proteomic and Lipidomic Approach
9 affiliations
- 1CIBB—Centre for Innovative Biomedicine and Biotechnology, CNC-UC—Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal
- 2CIVG—Vasco da Gama Research Center, EUVG-Vasco da Gama University School, 3020-210 Coimbra, Portugal
- 3i3S—Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal
- 4Associate Laboratory i4HB, Institute for Health and Bioeconomy, University Institute of Health Sciences—CESPU, 4585-116 Gandra, Portugal
- 5UCIBIO—Applied Molecular Biosciences Unit, Toxicologic Pathology Research Laboratory, University Institute of Health Sciences (1H-TOXRUN, IUCS-CESPU), 4585-116 Gandra, Portugal
- 6Centro de Espetrometria de Massa & LAQV-REQUIMTE & Departamento de Química, Universidade de Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal
- 7Institute for Interdisciplinary Research, University of Coimbra, 3030-789 Coimbra, Portugal
- 8CESAM & Departamento de Química, Universidade de Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal
- 9Department of Biological Sciences, Faculty of Pharmacy (FFUP), University of Porto, 4050-313 Porto, Portugal
Abstract
Although glioblastoma stem cells (GSCs) constitute a small subpopulation of this highly heterogeneous brain cancer, they are widely recognised as key drivers of tumour recurrence after surgical resection and resistance to radiotherapy and chemotherapy. Differentiation of GSCs has, therefore, emerged as a strategy to increase glioblastoma susceptibility to therapeutic and surgical interventions. Cellular and molecular heterogeneity of glioblastoma limits the effectiveness of any treatment that relies on single molecules identified as disease-specific biomarkers. In this context, lipidomic and proteomic profiles constitute a source of information that can be translated into the identification of clinically relevant diagnostic and prognostic biomarkers, and novel therapeutic targets towards eradication of this lethal disease. Our initial studies demonstrated that BMP4 induced differentiation of the human glioblastoma stem cells G144 with approximately a 30-fold increase in expression of the astrocytic marker GFAP, which was coupled with a reduction in cell proliferation (33% decrease in EDU incorporation), invasion (61% decrease) and tumoursphere growth (53% decrease in area), and enhanced senescence-associated β-galactosidase activity (5.9-fold increase). Lipidomic and proteomic analysis (using data from 3 and 4 independent experiments, respectively) was then performed, allowing the identification of specific lipids and proteins exclusively detected or predominant in stem or differentiated G 144 cells. Importantly, our findings, which revealed a 6-fold increase in GFAP expression upon downregulation of a specific protein detected only in stem cells (SPRY4), pave the way for the employment of the RNAi-mediated knockdown strategy as a mechanistically distinct alternative to the use of BMP4, and highlight this protein as a candidate regulator associated with the G144 stem-like phenotype.
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BibTeX
@article{cardoso2026differentiation,
title = {{Differentiation of Human Glioblastoma Stem Cells as a Prospective Tool to Find New Biomarkers and Molecular Targets: A Proteomic and Lipidomic Approach}},
author = {Ana M. Cardoso and Diana Serra and Cristina P. R. Xavier and João P. Monteiro and Catarina M. Morais and Isabel M. Nunes Correia and Maria do Rosário M. Domingues and M. Helena Vasconcelos and Amália S. Jurado and Maria C. Pedroso de Lima},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27219517},
url = {https://www.mdpi.com/1422-0067/27/21/9517},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Differentiation of Human Glioblastoma Stem Cells as a Prospective Tool to Find New Biomarkers and Molecular Targets: A Proteomic and Lipidomic Approach
AU - Ana M. Cardoso
AU - Diana Serra
AU - Cristina P. R. Xavier
AU - João P. Monteiro
AU - Catarina M. Morais
AU - Isabel M. Nunes Correia
AU - Maria do Rosário M. Domingues
AU - M. Helena Vasconcelos
AU - Amália S. Jurado
AU - Maria C. Pedroso de Lima
PY - 2026
DA - 2026/10/24
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219517
UR - https://www.mdpi.com/1422-0067/27/21/9517
AB - Although glioblastoma stem cells (GSCs) constitute a small subpopulation of this highly heterogeneous brain cancer, they are widely recognised as key drivers of tumour recurrence after surgical resection and resistance to radiotherapy and chemotherapy. Differentiation of GSCs has, therefore, emerged as a strategy to increase glioblastoma susceptibility to therapeutic and surgical interventions. Cellular and molecular heterogeneity of glioblastoma limits the effectiveness of any treatment that relies on single molecules identified as disease-specific biomarkers. In this context, lipidomic and proteomic profiles constitute a source of information that can be translated into the identification of clinically relevant diagnostic and prognostic biomarkers, and novel therapeutic targets towards eradication of this lethal disease. Our initial studies demonstrated that BMP4 induced differentiation of the human glioblastoma stem cells G144 with approximately a 30-fold increase in expression of the astrocytic marker GFAP, which was coupled with a reduction in cell proliferation (33% decrease in EDU incorporation), invasion (61% decrease) and tumoursphere growth (53% decrease in area), and enhanced senescence-associated β-galactosidase activity (5.9-fold increase). Lipidomic and proteomic analysis (using data from 3 and 4 independent experiments, respectively) was then performed, allowing the identification of specific lipids and proteins exclusively detected or predominant in stem or differentiated G 144 cells. Importantly, our findings, which revealed a 6-fold increase in GFAP expression upon downregulation of a specific protein detected only in stem cells (SPRY4), pave the way for the employment of the RNAi-mediated knockdown strategy as a mechanistically distinct alternative to the use of BMP4, and highlight this protein as a candidate regulator associated with the G144 stem-like phenotype.
SN - 1422-0067
ER -