TMIC-40. BIOPHYSICAL ANALYSIS OF GLIOBLASTOMA CORE AND RIM REVEAL UNIQUE MECHANICAL AND ULTRASTRUCTURAL SIGNATURES

Abstract

Abstract Glioblastoma (GBM) is a highly aggressive and invasive brain cancer, carrying a median survival of 15 months. This poor prognosis is due, in part, to its resistance to therapy through tumor adaptations mediated by the tumor microenvironment (TME). Efforts to describe the tumor-protective cues in the TME may aid in the development of strategies to combat resistance. Emerging work has indicated that GBM biophysical properties are significant modulators of tumor progression; however, these parameters are poorly described. Here, we investigate the mechanical, extracellular matrix (ECM), and ultrastructural characteristics of tumors in patient matched GBM core and rim tissue. Using atomic force microscopy, immunohistochemistry, and scanning electron microscopy techniques, we find that GBM core is abnormally stiff and dense with large amounts of ECM, while the rim is softer and more porous. The GBM core is uniquely rich in hyaluronic acid and Tenascin-C, ECM proteins known to correlate with tumor stiffness and tumor supportive function. Additionally, dense matrix along with increased levels of hyaluronic acid and Tenascin-C correlate with decreased progression free survival. These data suggest that the stiff core provides increased pro-malignant mechanotransductive cues while the rim presents more permissive routes for GBM invasion. These results reveal a biophysical basis for tumor progression and provides a novel framework for diagnostic strategies and therapeutic intervention.