Spatial vascular/BTB remodeling and malignant-state plasticity in glioblastoma
Background: Glioblastoma (GBM) contains spatially heterogeneous malignant and vascular states, but blood-tumor barrier (BTB) remodeling is often described as a binary functional phenotype. We asked whether anatomically distinct GBM compartments contain separable vascular programs that coexist with malignant-state plasticity. Methods: We performed donor-aware cross-sectional analyses of 38…
Glioblastoma (GBM) exhibits spatially diverse malignant and vascular states, but blood-tumor barrier (BTB) remodeling is typically considered a binary functional trait. Researchers questioned whether different regions within GBM contain distinct vascular programs coexisting with malignant-state plasticity. Analyzing 38 spatially annotated histopathology sections from six donors, they found that THSD1-FLT4 Recognition increased from the tumor's leading edge to infiltrative areas, while priming increased across this boundary but decreased from infiltrative to cellular tumor regions.
Gate remodeling, on the other hand, increased from infiltrative to cellular tumor regions. Remodeled endothelium showed higher PLVAP detection and pseudobulk expression, but lower MFSD2A pseudobulk expression. External cohorts further validated regional vascular/BTB remodeling, and GSE131928 provided broader malignant-state architecture data.
The study concluded that GBM contains spatially segregated vascular/BTB-associated programs alongside malignant-state plasticity, with Recognition-Priming-Gate being a cross-sectional discovery framework rather than a validated temporal cascade. The data did not establish BTB permeability, causal tumor-vascular signaling, or therapeutic delivery benefits.
Written by urgent.news from bioRxiv's reporting — not their text. Machine-written — may contain errors; check the original before relying on it.
