Abstract 3961: Influence of hyaluronic acid in tumor microenvironment on glioblastoma (GBM) invasive behavior

Glioblastoma invasion is mediated by distinct interactions between tumor cells and the extracellular matrix. Engineered biomaterial platforms allow for systemic examination of the influence of the microenvironment HA content on GBM cell activity. In this study, high molecular weight hyaluronic acid (700 kDa) was photopolymerized within three-dimensional (3D) polyethylene-glycol (PEG) hydrogels and patient-derived, primary GBM cell migration in the HA-hydrogels was investigated. Hydrogel polymerization conditions were tuned to achieve orthogonal control of HA content in a series of hydrogels (0.1 - 0.75 wt% HA) with conserved poroelastic properties (i.e. storage moduli and diffusivity). GBM cell migration was strongly influenced by microenvironment HA content. Knockdown of HA-dependent cell surface receptors (CD44 and RHAMM) modulated GBM cell activity. Our results demonstrate that alterations in microenvironment HA content and inhibition of HA-dependent signaling produced distinct molecular and phenotypic differences in GBM migratory behavior. These results demonstrate the differential effect of tumor microenvironment HA content on the invasive phenotype of GBM in a physiologically relevant 3D culture environment. Citation Format: Itay Solomon, Alireza Sohrabi, Stephanie K. Seidlits. Influence of hyaluronic acid in tumor microenvironment on glioblastoma (GBM) invasive behavior [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 3961.