ESTABLISHMENT OF A MURINE MODEL FOR METASTASIS OF CYTOKINE-PRODUCING TUMOR TO THE BRAIN

The A375 cell line, derived from human malignant melanoma, has charact eristics of interleukin-6 (IL-6) production. By using this cell line, we have investigated a murine metastasis model of IL-6-producing tumor s to the brain by injecting A375 cells directly into the left cardiac ventricle. Nude mice were anesthetized with intraperitoneal injection of pentobarbital sodium. Next, A375 cells suspended in phosphate-buffe red saline (PBS) were injected into the left cardiac ventricle of mice . An intracardiac injection of 10(5) cells developed tumor colonies in the brain after 4 to 6 weeks. Metastatic cells were found in every lo be of the brain. An immunocytochemical study revealed IL-6 production by A375 cells at the metastatic sites in the brain. By the transfectio n of genes encoding proteins into A375 cells, a novel model of protein expression in the brain in vivo could be constructed. Our system does not require great skill. Our experimental model will facilitate futur e studies of the local effects of proteins in the brain.