STEM-22. EFFECT OF A SRC INHIBITORY PEPTIDE BASED ON CONNEXIN43 ON NEURAL STEM CELLS WITH GLIOMA-DRIVER MUTATIONS

Abstract Glioblastomas are one of the most malignant tumors. Glioma Stem Cells (GSCs) a subpopulation cells resistant to standard treatments, responsible for tumor recurrence. Strong evidence supports that Neural (NSCs) from subventricular zone (SVZ) origin GSCs. This transition frequently concurs with epidermal growth factor receptor (EGFR) overexpression or mutations, such as EGFRvIII. Our group designed cell penetrating peptide based on connexin43 (TAT-Cx43266-283) inhibits oncoprotein c-Src and therefore targets GSCs, increasing survival in glioma-bearing mice. Because EGFR signaling closely related, we explored effect TAT-Cx43266-283 NSCs We compared TAT-Cx43266-283, control peptides, temozolomide erlotinib, common inhibitor, SVZ (Control-NSCs) murine NSC patient-derived GSCs key glioma-driver mutations Nf1, PTEN EGFR. pathway was analyzed by Western blot. Furthermore, analyzing mouse model where tumors originate mutations. results showed strong viability amplification active EGFRvIII, without significant effects Control-NSCs. Importantly, found lower temozolomide, other peptides these cells. blot analyses suggest decreases EGFR, EGFRvIII activity. Preliminary vivo size enhances mice bearing gliomas initiated altered NSCs. So far, our show impairs subsequent reduction proliferation alterations. These stress relevance future therapy against glioblastoma, alone combination treatments.