A Quantitative Analysis of Vascularization and Perfusion of Human Glioma Xenografts at Different Implantation Sites

The effect of tissue site of implantation of four different human gliomas on tumor vascularity and perfusion was examined. Vascular parameters of gliomas implanted subcutaneously in the nude mouse and intracerebrally in the nude rat were analyzed. Tumor vessels were stained with an antibody to collagen type IV and perfusion was investigated with the perfusion marker Hoechst 33342. Characteristic vascular patterns were observed in both intracerebral and subcutaneous xenografts belonging to the same tumor line. Major differences in vascular architecture and in the degree of vascularization were noted in comparisons of the two implantation sites for the same tumor line. Tumor perfusion was highly variable for both locations of tumor growth. Distinct differences between the implantation sites of similar tumor lines in vascular perfusion, intervascular distance, and vascular density were present. Incomplete perfusion of vascular structures, as seen in this study, may result in reduced delivery of oxygen to tumor areas. Therefore, measurements of vascular density and intervascular distance alone, without knowledge of the perfusion status, may not be sufficient to estimate the degree of tumor oxygenation. Furthermore, differences in vascular parameters may have important consequences for treatment modalities such as radiotherapy and chemotherapy. Thus, the findings in our study suggest that care has to be taken in extrapolating therapy results obtained with subcutaneous glioma tumor models to the original growth location of gliomas, the brain, due to major differences in vasculature.