Following 26 MRI-guided glioma biopsies in these 11 patients, we evaluated tissue morphometry, including vessel density and average radius, using an automated procedure based on the endothelial cell marker CD31 to highlight tumor vasculature.
DIPGs are vascularized tumors and interestingly, REST loss in DIPG cells also caused a substantial decline in tumor vasculature as measured by a decrease in CD31 and VEGFR2 staining.
Furthermore, mouse models showed that baicalein reduced the tumor volume and greatly reduced the tumor growth rate in the early stages of tumor progression, and the baicalein-treated groups had significantly reduced expression of CD31 (endothelial cell marker) and α-SMA (mural cell marker) in the tumors, indicating that baicalein inhibits tumor angiogenesis by disrupting tumor vasculature development.
Immunohistochemical analysis of VEGFR-2 and CD31 supported SPECT and autoradiographic imaging findings, revealing the corresponding depletion of VEGFR-2- and CD31-positive endothelial cells from tumor vasculature during therapy and the rapid reemergence of VEGFR-2- and CD31-positive vasculature at the tumor edges after discontinuation of treatment.
Expression of CD31 and platelet-derived growth factor receptor-beta (PDGFR-beta) in the tumor vasculature by immunohistochemistry was significantly associated with response (PR versus SD/PD; CD31 median, 33.5 versus 13.2; P = 0.0004; PDGFR-beta median, 5.9 versus 0.6; P = 0.01).
However, increased CD31 expression and morphological changes representative of sinusoidal capillarization in tumor vasculature indicate that vascular remodeling is taking place.