Specificity of Aptamers U2 and Gol1 to EGFR-Positive Human Glioblastoma Cells in Vitro

Overexpression of epidermal growth factor receptor (EGFR) and its mutations influence signal pathways leading to the proliferation, invasion, and increased survival of tumor cells. Despite the successful clinical application of antibodies against EGFR in patients with colorectal cancer and squamous cell carcinoma of the head and neck, these have been found to have low efficacy in glioblastoma. The treatment of gliomas therefore requires an EGFR-specific drug able to penetrate the tumor focus in the brain and which has low immunogenicity. We report here studies of aptamers (single-stranded DNA oligonucleotides) specific to EGFR, U2, and Gol1 and discuss their use as agents of this type. The work reported here includes preparation of a cell model of human glioma with overexpression of EGFR and EGFRvIII and its use to demonstrate the specificity of aptamers U2 and Gol1 to these receptors using classical methods and by apta-immunocytochemistry. Investigation of the effect of binding of aptamer Gol1 to the EGFRvIII receptor on subsequent steps in the signal pathway demonstrated changes in the levels of expression of genes associated with cell proliferation and survival [ Jun , Fos , CCND1 , PI3K and Akt3 ], while aptamer U2 did not produce any significant effect on cells in vitro. These results indicate that Gol1 aptamer has therapeutic potential against human glioblastoma tumor cells overexpressing the mutant EGFRvIII receptor.