The growth of two murine hemangioendotheliomas intracranially, subcutaneously, and in culture, and their comparison with human cerebellar hemangioblastomas: morphological and immunohistochemical studies

Abstract

Two thorium dioxide-induced murine hemangioendotheliomas, 42021 TCT and 44347 TST, were grown subcutaneously (for up to 22 and 15 passages respectively) or intracranially (single passage) and were adapted to culture as a monolayer and, in a limited fashion, in an organ culture system or in rotary suspension. They remained viable and malignant following 20-21 years of storage in liquid nitrogen, and had ultrastructural similarities to human hemangioblastomas. The murine tumors were positive for Griffonia (Bandeiraea) simplicifolia isolectin B4 binding, establishing their endothelial nature; however, unlike human hemangioblastic tumors, they did not cross-react with antisera to human factor VIII or fibronectin and they did not demonstrate Ulex europaeus type I lectin (UEA I) binding (as is also the case for non-neoplastic murine vascular endothelial cells). A variety of morphological cell types in cultures derived from the tumors were also positive for Griffonia (Bandeiraea) simplicifolia isolectin B4 binding. Both murine hemangioendotheliomas, when implanted in the cerebrum, were potent inducers of reactive gliosis, but there was no evidence of uptake of glial fibrillary acidic protein. Unlike the human cerebellar hemangioblastomas, murine tumors were malignant and invasive and did not contain stromal cells, nor did they demonstrate Weibel-Palade bodies or extensive pinocytotic activity. Thus, the murine tumors appear to more closely resemble angiosarcomas or epitheloid hemangioblastomas than the cerebellar hemangioblastomas.