EXPERIMENTAL PULMONARY SARCOMA METASTASES IN ATHYMIC NUDE-MICE

Background: Pulmonary metastases remain a challenging therapeutic prob lem in the treatment of patients with soft tissue sarcomas. A pulmonar y sarcoma metastases animal model might facilitate studying the biolog y of metastases, diagnosis, and treatment modalities of this disease. Intravenous injection of human tumor cells into nude mice has been rep orted using human melanoma and colorectal carcinoma to produce pulmona ry metastases. Human fibrosarcoma cells were intravenously administere d to athymic nude mice to simulate clinical pulmonary metastases. Meth ods: 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 subcutaneousl y 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 microsc opic spontaneous metastases were found in any of the animals that rece ived subcutaneous xenografts, and no pulmonary metastases were identif ied in mice intravenously injected with <10(5). All mice inoculated wi th 10(6) cells developed tumor colonies in the lungs, which were micro scopically evident as early as day 7. No metastases were found in the liver, spleen, heart, or other tissues. In a second experiment, HT-108 0 cells were injected at 10(6); all animals developed lung metastases and died of lung tumor involvement, with an average survival of 35 day s. Conclusions: These experiments identify a sarcoma animal pulmonary metastases model that is readily available, relatively inexpensive, ea sily utilized, and reproducible. (C) 1997 Wiley-Liss, Inc.