Abstract 6152: Characterizing cancer stem cells in diffuse intrinsic pontine glioma

Abstract

Abstract Diffuse Intrinsic Pontine Glioma (DIPG) is a lethal pediatric brain cancer with a five-year survival rate of less than 1%. This is reflective of a 100% tumor reoccurrence emphasizing the need for efficacious therapies. Previous studies have identified Aldehyde dehydrogenase expression (ALDH) as a marker for stemness and an indicator of tumor aggression and therapeutic resistance in many malignancies including adult glioma. Understanding the role of cancer stem-cells in gliomagenesis of DIPG is critical for developing therapies targeting resistance and averting 200-400 pediatric deaths in the US per year. We identified a subpopulation of cells expressing the ALDH cancer stem-cell marker in patient-derived DIPG cell lines with high variability in ALDH expression among the cell lines likely indicating previous treatment and resistance. As expected, proliferation and neurosphere formation as well as neurosphere size were dramatically increased in ALDH+ CSC compared to ALDH- CSC supporting our hypothesis of a tumor initiating, aggressive subpopulation likely conferring therapeutic resistance. To evaluate tumor initiation properties of ALDH+ CSC subpopulation in vivo, implantation of SU-DIPG-7 luciferase expressing cells into the pons of immunocompromised mice (NSG) was performed after sorting for ALDH by FACS. Our results demonstrate tumor initiation and tumor growth in ALDH+ mice as assessed by Bioluminescence imaging (BLI) as well as histological analysis. Furthermore, survival of mice implanted with ALDH+ CSCs was significantly reduced compared to mice implanted with ALDH- cells indicating tumor initiating and ‘stem cell' properties of this subpopulation. In summary, we have identified and characterized ALDH+ cancer stem-cells in DIPG which are more aggressive than the non-cancer stem-cell population (ALDH-). These results highlight the need to develop therapies targeting this highly aggressive cancer stem-cell population. Future studies investigating the gene regulation response to treatment in these stem-cell subpopulations could provide valuable insight to co-targeted therapies to address treatment resistance in DIPG. Citation Format: Sarah F. Ferris, Rachel K. Surowiec, Carlos Espinoza, Stefanie Galban. Characterizing cancer stem cells in diffuse intrinsic pontine glioma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6152.