Experimental pulmonary sarcoma metastases in athymic nude mice.

BACKGROUND: Pulmonary metastases remain a challenging therapeutic problem in the treatment of patients with soft tissue sarcomas. A pulmonary sarcoma metastases animal model might facilitate studying the biology of metastases, diagnosis, and treatment modalities of this disease. Intravenous injection of human tumor cells into nude mice has been reported using human melanoma and colorectal carcinoma to produce pulmonary metastases. Human fibrosarcoma cells were intravenously administered to athymic nude mice to simulate clinical pulmonary metastases.
METHODS: HT-1080 human sarcoma cells derived from a poorly differentiated fibrosarcoma were used to prepare inoculant at a concentration of 5 x 10(6) cells per ml. Male athymic nude mice were injected subcutaneously with 1 x 10(6) cells in the right hind flank and sacrificed when the tumors were 1-2 cm in diameter. Age- and weight-matched athymic nude mice were intravenously injected through tail veins with 10(4), 10(5), and 10(6) cells. The mice were sacrificed at 7, 14, and 21 days after intravenous injection of the tumor cells. Tissues were histologically examined for pulmonary metastases.
RESULTS: Neither gross nor microscopic spontaneous metastases were found in any of the animals that received subcutaneous xenografts, and no pulmonary metastases were identified in mice intravenously injected with < 10(5). All mice inoculated with 10(6) cells developed tumor colonies in the lungs, which were microscopically evident as early as day 7. No metastases were found in the liver, spleen, heart, or other tissues. In a second experiment, HT-1080 cells were injected at 10(6); all animals developed lung metastases and died of lung tumor involvement, with an average survival of 35 days.
CONCLUSIONS: These experiments identify a sarcoma animal pulmonary metastases model that is readily available, relatively inexpensive, easily utilized, and reproducible.