An experimental model for cerebral metastasis: preliminary light and ultrastructural studies.

An experimental model for hematogenously spread cerebral metastases by injection of a suspension of M3 fibrosarcoma cells into the carotid artery of C57 BL/6 mice was developed. Intracerebral metastatic tumor nodules were consistently produced by this method with subsequent death of the animals. Development of extracerebral metastatic disease was minimal. Light and electron microscopic studies were carried out at various time intervals postintracarotid injection of tumor cells to observe the morphologic events during the development of the brain metastases. Tumor cells were observed arrested in the cerebral capillaries from 15 minutes to 4 days post-injection. From 1 day to 4 days post-injection, individual tumor cells were also observed in the pericapillary spaces in the brains of the injected animals. From 5 days post-injection on, tumor cells were seen to be proliferating in peri-capillary spaces displacing the brain parenchyma and eventually formed tumor nodules with resulting death of the animals. Morphological changes were observed in the endothelial cells of the blood vessels which were surrounded by the growing metastatic tumors. This model, and modifications thereof, should prove to be valuable in the study of cerebral metastatic disease.