Endothelial differentiation in intracerebral and subcutaneous experimental gliomas

Blood-brain barrier (BBB) properties of endothelial cells have on impact on brain tumor behavior, diagnosis, and response to therapy. Biochemical BBB properties are expressed by endothelial cells within intracerebral (IC) gliomas but little is known regarding the expression of BBB-associated proteins within gliomas established subcutaneously (SC), a site that is frequently used in experimental glioma models. We compared the expression of two BBB proteins, glucose transporter type-1 (Glut1) and endothelial barrier antigen (EBA), in IC and SC rat 9L and F98 gliomas. The percentage of microvessels with immunohistochemically-detectable Glut1 and EBA in IC 9L tumors (31-98%) contrasted with that found in SC 9L tumors (0-3.9%) (P < 0.0001). Likewise, the percentage of immunohistochemically-positive vessels in IC F98 tumors (35-66%) differed markedly from that in SC F98 tumors (0%) (P < 0.00001). These differences were not explained by effects of tumor location on vessel density or tumor histology. These findings demonstrate that the peritumoral environment influences endothelial differentiation within glial tumors and suggest that glioma cells maintain but do not induce the expression of barrier properties in vessels that infiltrate tumor from surrounding tissue.