Characterization of cellular plasticity of human GBM lines with stem cell properties using three-dimensional (3D) cultures.

VIDELA-RICHARDSON, GUILLERMO A.; HORACIO MARTINETTO; GUSTAVO SEVLEVER; BELFORTE FIORELLA; MORRIS OLIVIA; JOAQUÍN M ESPINOSA; LUCIA CANEDO; GUSTAVO MOSTOVLAVSKY, ; CAROLINA PEREZ CASTRO

Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencias 2017; 2017

The study of molecular and cellular mechanisms involved in the formation of tumors, which originate from cells that undergo "reprogramming", is critical to understand their characteristic functional heterogeneity and therapeutic resistance. In this category, Glioblastoma, a highly aggressive brain tumor, attacks the brain by infiltrating and making difficult for its surgical removal. We studied the plasticity of different established patient-derived human GBM cells using three-dimensional (3D) cultures as an experimental model system. Although different patient-derived lines presented heterogeneous expression levels of the both stemness markers CD133 and KANSL2, a consistent positive correlation between their expressions was found as well as their cell self-renewal capacity in the 3D cultures. The overexpressed KANSL2 cells showed induced transcriptional activation of developmental master genes and enhanced the initiator ability of tumor spheres validating its role as a positive regulator of tumor stem cell identity. Interestingly, using the different population of CD133 expression cells, we found that the migratory capacity of these cells with stem properties is inversely proportional to the levels of mesenchymal markers.A better understanding of the in vitro behavior of these cells will improve our knowledge for the development of new therapeutic pathways and their potential use for therapeutic screening.