Formation of PC12 tumors after transplantation into rat brains: dependence of time course on host age.

Abstract

Rat pheochromocytoma PC12 cells form tumors when placed into the brains of Sprague-Dawley rats under specific conditions. We now show that tumorigenic potential is regulated by the microenvironment of the developing cerebrum. PC12 cell aggregates were identified in the periventricular or intraventricular spaces within 24 h after injection of cell suspensions into rat brains. In fetal or young neonatal (1-4-day-old) recipient rat brains, these cell aggregates formed large masses within 21 days. The tumor incidence declined in recipient neonates between the ages of 5 and 8 days. In both cases, tumors spread throughout the ventricular system and subarachnoid and Virchow-Robin spaces as they grew. In contrast, tumors were not generated by injections into adult rat brains or by placement of PC12 cell pellets into preformed cavities. Despite the loss of tumorigenicity, surviving cells were present at the injection site. The presence of surviving cells and the ability of another rat cell line (the C6 rat glioma line) to form tumors in adult rat brains suggest that an immune response is not solely responsible for the lack of PC12 tumorigenicity in adult rat brains. We propose that developmentally increasing local concentrations of specific factors (e.g., nerve growth factor of fibroblast growth factor) may also contribute to the suppression of tumor formation in this system.