Suramin treatment of human glioma xenografts; effects on tumor vasculatureand oxygenation status

In this study the effect of suramin on tumor growth, vascularity and oxygen ation of a human glioma xenografted in the nude mouse was examined. Vascula r parameters and oxygenation status of the xenografts were determined immun ohistochemically in frozen sections of the tumors, using the hypoxia marker pimonidazole-hydrochloride to detect hypoxic areas. Tumor vessels in these sections were stained by an endothelial cell marker and perfusion of vesse ls was visualized by administration of the perfusion marker Hoechst 333342 before harvesting the tumors. The vascular parameters were quantified with an image analysis system. The results show that tumor growth was reduced co nsiderably after suramin treatment. This growth suppression was accompanied by marked changes in vascular architecture. Although the total vascular ar ea and perfused fraction of tumor vessels remained unchanged after suramin treatment, vascular density increased, indicating that more but smaller ves sel structures had developed during therapy. These vessel structures were a lso more homogeneously spread over the tumor area. Control tumors showed ex tensive areas of hypoxia while in treated tumors hypoxic areas had mostly d isappeared. This effect was probably due to the higher density of homogeneo usly distributed perfused vessel structures in the treated tumors, contribu ting to an increased oxygenation of the tumor. These observations suggest t hat suramin therapy can result in marked changes not only in tumor vascular ity but also in tumor oxygenation status which may have important consequen ces for sensitivity of these tumors to other therapies such as radiation tr eatment.