Metastasis from the brain of transplanted N-ethyl-N-nitrosourea-induced central nervous system tumors in rats

Two transplantable rat central nervous system (CNS) tumors induced by N-ethyl-N-nitrosourea (ENU) were employed to study the mechanisms controlling extracranial metastasis from intracranial tumors. Cells derived from a serially passaged anaplastic astrocytoma and a malignant glioma were injected intracerebrally at doses of 10⁴, 10⁵ and 10⁶ cells per rat (Sprague-Dawley and WAG/Rij rats). As soon as neurological dysfunction appeared, animals were sacrificed and examined histologically for (1) extracerebral outgrowth of the intracerebral tumor, (2) the presence of distant metastases within the CNS and (3) remote metastases outside the CNS. In addition to histology, a bioassay procedure was performed. Metastases were found in cervical lymph nodes (74%), lung (21%) and liver (5%). For both tumor groups, rats with both distant CNS metastases and local extracerebral outgrowth developed remote metastases more frequently (P < 0.05) than animals with intracerebral growth only. The data indicate that both local extracranial spread due to surgical intervention as well as local and distant invasion of leptomeninges promote extracranial metastatic spread.