Nucleolin is expressed in patient-derived samples and glioblastoma cells, enabling improved intracellular drug delivery and cytotoxicity

作者：Balca Silva Joana; do Carmo Analia; Tao Herminio; Rebelo Olinda; Barbosa Marcos; Moura Neto Vivaldo; Sarmento Ribeiro Ana Bela; Lopes Maria Celeste; Moreira Joao Nuno^*

来源：Experimental Cell Research, 2018, 370(1): 68-77.

DOI：10.1016/j.yexcr.2018.06.005

• Glioblastoma
• Glioblastoma stem-like cells
• Nucleolin
• Therapeutic Target

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.

• 出版日期2018-9-1