Journal
EXPERIMENTAL CELL RESEARCH
Volume 370, Issue 1, Pages 68-77Publisher
ELSEVIER INC
DOI: 10.1016/j.yexcr.2018.06.005
Keywords
Glioblastoma; Glioblastoma stem-like cells; Nucleolin; Therapeutic Target
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Funding
- Inter-University Doctoral Program in Aging and Chronic Diseases
- Portuguese Foundation for Science and Technology (FCT) [SFRH/BD/51993/2012]
- European Regional Development Fund (ERDF), through COMPETE 2020 - Operational Program for Competitiveness and Internationalization and Portuguese national funds via FCT - Fundacao para a Ciencia e a Tecnologia [POCI-01-0145-FEDER-007440]
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One of the major challenges in Glioblastoma (GBM) therapy relates with the existence of glioma stem-like cells (GSCs), known to be chemo- and radio-resistant. GSCs and non-stem GBM cells have the ability to interchange, emphasizing the importance of identifying common molecular targets among those cell sub-populations. Nucleolin overexpression has been recently associated with breast cancer sub-populations with different stem like phenotype. The goal of this work was to evaluate the potential of cell surface nucleolin as a target in GBM cells. Different levels of nucleolin expression resulted in a 3.4-fold higher association of liposomes targeting nucleolin (functionalized with the nucleolin-binding F3 peptide) in U87, relative to GBM11 glioblastoma cells. Moreover, nucleolin was suggested as a potential marker in OCT4-, NANOG-positive GSC, and in the corresponding non-stem GBM cells, as well as in SOX2-positive GSC. Doxorubicin delivered by liposomes targeting nucleolin enabled a level of cytotoxicity that was 2.5- or 4.6-fold higher compared to the non-targeted counterparts. Importantly, an overexpression of nucleolin was also observed in cells of patient-derived samples, as compared with normal brain. Overall, these results suggested nucleolin as a therapeutic target in GBM.
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