Biologic and immunologic studies on a murine model of regional lymph node metastasis

Some biologic, hematologic, and immunologic aspects of the growth and metastasis of the MC-2 fibrosarcoma indicated its suitability as a model for the study of lymphogenous metastasis. The tumor was maintained in syngeneic female BALB/c mice by the serial sc passage of 10(5) viable tumor cells. It metastasized macroscopically in all mice to regional lymph nodes (RLN) and to the lungs. Both forward and retrograde node-to-node metastases were found. Tumor growth and metastasis were associated with splenomegaly, thymus atrophy, cachexia, neutrophilia, lymphopenia, and anemia. Tumor excision at various times after inoculation showed that all mice whose tumors were excised when there was histologic evidence of metastasis in all RLN (day 13; mean of tumor wt, 122 mg) died subsequently from metastases, whereas no animals died whose tumors were excised on or before day 8 (mean of tumor wt, 15 mg). The onset of metastasis was seen in some RLN on day 8. All survivors were immune to challenge with 10(5) viable tumor cells, which demonstrated the immunogenicity of the tumor. Concomitant tumor immunity could be demonstrated prior to the onset of metastasis (days 6 and 7) but not early (days 0--2) or late (days 15, 19, and 20) in primary-site tumor growth. The early immune response to the tumor demonstrable as concomitant tumor immunity appeared to be abrogated by the progressive growth and metastasis of the neoplasm. Tumor cells passaged in adult thymectomized, X-irradiated, syngeneic recipients produced larger RLN metastases and smaller primary tumors than those passaged in control mice.