TMIC-119. Evaluating the Impact of Tumor-Secreted Fibronectin-1 on the Perivascular Niche (PVN) and Glioblastoma Malignancy

Abstract Glioblastoma multiforme (GBM) is an aggressive brain tumor characterized by poor prognosis and frequent recurrence. The tumor microenvironment (TME) plays a crucial role in GBM progression, with extracellular matrix (ECM) components like Fibronectin (FN1) supporting tumor growth and invasion. This study investigated the impact of FN1 on microvascular alterations in GBM. Patient-derived specimens and mouse glioma models were classified as ECM-high or ECM-low based on FN1 expression. Histopathological and immunofluorescence analyses were performed on formalin-fixed, paraffin-embedded (FFPE) tumor sections. The results showed the FN1-high tumors exhibited more aggressive features, including palisading necrosis, mesenchymal regions, and enhanced vascular proliferation. FN1-high tumors showed elevated pericyte (SMA+) and endothelial cells (CD31+) proliferation, reinforcing their aggressive phenotype. Additionally, FN1-high tumors showed enrichment of astrocytes with GFAP+ expression surrounding the perivascular niche (PVN) but not tumors with low FN1 expression. Histopathological evaluation of FN1-high gliomas also showed a higher density of defined Vascular Garland and Glomeruloid vascular proliferation patterns compared to FN1-low tumors, which displayed less malignant vascular patterns like Microvascular Sprouting and Vascular Cluster. These results suggest that GBM cells overexpressing FN1 are associated with more malignant microvascular patterns and increased pericyte and endothelial proliferation. This study highlights the potential of glioma-secreted FN1 components as pathological biomarkers and therapeutic targets for mitigating GBM malignancy.