Intracranial injection of human meningioma cells in athymic mice: an orthotopic model for meningioma growth

Object. Although human meningioma cells have been heterotopically implanted in nude mice, introducing these cells into intracranial locations seems mo re likely to reproduce normal patterns of tumor growth. To provide an ortho topic xenograft model of meningioma, the authors implanted a controlled qua ntity of meningioma cells at subdural and intracerebral sites in athymic mi ce. Methods. Malignant tone tumor), atypical (two tumors), or benign (three tum ors) meningiomas were placed into primary cell cultures. Cells (10(6)/10 mu l) from these cultures and from an immortalized malignant meningioma cell line, IOMM-Lee, were injected with stereotactic guidance into the frontal w hite matter or subdural space of athymic mice. Survival curves were plotted for mice receiving tumor cells of each histological type and according to injection site. Other mice were killed at intervals and their heads were se ctioned whole. Hematoxylin and eosin staining of these sections revealed th e extent of tumor growth. Conclusions. The median length of survival for mice with malignant, atypica l, or benign tumors was 19, 42, or longer than 84 days, respectively. Atypi cal and malignant tumors were invasive, but did not metastasize extracrania lly. Malignant tumors uniformly showed leptomeningeal dissemination and tho se implanted intracerebrally grew locally and spread noncontiguously to the ventricles, choroid plexus, convexities, and skull base. Tumors formed in only 50% of mice injected with benign meningioma cells, whereas injection o f more aggressive cells was uniformly successful at tumor production. The t hree types of human meningiomas grown intracranially in athymic mice mainta ined their relative positions in the spectrum of malignancy. However, atypi cal meningiomas became moro aggressive after xenografting and acquired mali gnant features, implying that there had been immune constraint in the origi nal host. Tumor cells injected into brain parenchyma migrated to more optim al environments and grew best there. This model provides insights into the biology of meningiomas and may be useful for resting new therapies.