Associação Portuguesa de Investigação em Cancro
Nucleolin expression improved intracellular drug delivery in glioblastoma cells
Nucleolin expression improved intracellular drug delivery in glioblastoma cells
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. In our work, nucleolin overexpression in GBM cells resulted in a higher association of liposomes targeting nucleolin. Moreover, nucleolin was suggested as a potential marker in GSCs, and in the corresponding non-stem GBM cells. Doxorubicin delivered by liposomes targeting nucleolin enabled a higher level of cytotoxicity. 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.
Authors and Affiliations:
Balça-Silva J1, do Carmo A2, Tão H3, Rebelo O4, Barbosa M5, Moura-Neto V6, Sarmento-Ribeiro AB7, Lopes MC8, Moreira JN9
1 CNC.IBILI - Center for Neuroscience and Cell Biology and Institute for Biomedical Imaging and Life Sciences, Coimbra, Portugal; FMUC - Faculty of Medicine, University of Coimbra, Coimbra, Portugal; IECPN - Instituto Estadual do Cérebro Paulo Niemeyer, Secretaria de Estado de Saúde, Rio de Janeiro, Brazil;
2 CNC.IBILI - Center for Neuroscience and Cell Biology and Institute for Biomedical Imaging and Life Sciences, Coimbra, Portugal; CHUC - Clinical Pathology Department, Coimbra Hospital and Universitary Center, Coimbra, Portugal;
3 CHUC - Neurosurgery Service, Coimbra Hospital and Universitary Center, Coimbra, Portugal;
4 CHUC - Neuropathology Laboratory, Neurology Service, Coimbra Hospital and Universitary Center, Coimbra, Portugal;
5 FMUC - Faculty of Medicine, University of Coimbra, Coimbra, Portugal; CHUC - Neurosurgery Service, Coimbra Hospital and Universitary Center, Coimbra, Portugal;
6 IECPN - Instituto Estadual do Cérebro Paulo Niemeyer, Secretaria de Estado de Saúde, Rio de Janeiro, Brazil;
7 FMUC, Laboratory of Oncobiology and Hematology and University Clinic of Hematology/ Faculty of Medicine, University of Coimbra, Coimbra, Portugal; iCBR, CIMAGO - Coimbra Institute for Clinical and Biomedical Research - Group of Environment, Genetics and Oncobiology - FMUC, Coimbra, Portugal; CHUC - Clinical Hematology Department/Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal; CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal;
8 CNC.IBILI - Center for Neuroscience and Cell Biology and Institute for Biomedical Imaging and Life Sciences, Coimbra, Portugal; FFUC - Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal;
9 CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; FFUC - Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal.
Abstract:
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.
Journal: Experimental Cell Research
Link: https://www.ncbi.nlm.nih.gov/pubmed/29902537