Abstract 3965: Novel biomimetic, interfacing 3D hydrogels to investigate roles of glioblastoma (GBM) niche on GBM progression

Glioblastoma (GBM) is the most common and lethal form of brain tumors with survival rate of 5% after 5 years. In the tumor microenvironment, invading GBM cells experience various ECM transitions at the tumor margin, such as alterations in matrix stiffness. Although conventional three-dimensional (3D) hydrogels have improved upon existing in vitro tumor models, these biomaterial platforms are not capable of separating the migratory GBM population from the bulk of the tumor. In addition, conventional hydrogels can only mimic a single microenvironment property (i.e. stiffness and protein presentation). In this study, we fabricated interfacing hyaluronic acid (HA)-based hydrogels using thiol-ene photochemistry to mimic the distinct stiffness conditions of tumor and surrounding tissue as well as the stiffness transition. The novel interfacing model enabled us to isolate invading GBM cells for further in vitro analysis. Atomic Force Microscopy (AFM) analysis of our xenograft GBM tumors in mice brain demonstrated that GBM tumor is stiffer than surrounding brain tissue. Therefore, mechanical properties of each hydrogel condition were characterized via AFM to confirm similarity of hydrogel stiffness to GBM xenografts and patient-derived, primary GBM cell migration in the HA-hydrogels was investigated. Immunohistochemistry staining showed that invading GBM cells, passing the interface have higher expression of RHAMM and CD44. Our findings suggest that invading GBM cells might have different expression profile and therefore require more thorough analyses using single cell RNA-seq. Citation Format: Alireza Sohrabi, Jesse Liang, Gevick Safarians, Elnaz Guivatchian, Itay Solomon, Stephanie Seidlits. Novel biomimetic, interfacing 3D hydrogels to investigate roles of glioblastoma (GBM) niche on GBM progression [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 3965.