Abstract 2021: A novel model to study the stroma-induced drug resistance in glioblastoma cells

Glioblastomas (GBMs) are lethal cancers with a limited response to chemotherapies. In order to study whether stromal cells convey drug resistance to glioma cells, we have established a 3 D glioma cell-specific bioluminescence assay which mimics the growth of glioma in vivo and allows for direct measurements of tumor cell viability. With lentiviral transfection experiments we have provided a panel of human glioma cell lines stably expressing the luciferase reporter gene. Luciferase expression was proportional to the number of glioma cells, but not influenced by the presence of stromal cells. This way, Luciferase signal detection could be used to monitor glioma cell viability following treatment. Glioma cells alone or cultured with stromal cells can form 3 D spheroids, then treated with Temozolomide and Doxorubicin. Through comparative analysis, stromal cells influenced the sensitivity of different chemotherapy drugs in several glioma cell lines. Experiment also proved bioluminescence assay was more sensitive than MTS assay in co-culture system. This glioma cell-specific bioluminescence platform possibly provided a tool to screen stroma-induced changes in anti-tumor drug activity. Using the platform, we will be able to screen FDA-approved drugs on different glioma cell lines and biopsies, which will potentially guide the selection of tumor associated stromal specific targets for therapeutic validation. Citation Format: Ning Yang, Huaiyang Zhu, Tao Yan, Xiao Liang, Lina Wik Leiss, Per Øyvind Enger, Xingang Li, Jian Wang. A novel model to study the stroma-induced drug resistance in glioblastoma cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2021. doi:10.1158/1538-7445.AM2014-2021