Immunologically nonspecific enhancement of artificial lung metastases in tumor-bearing mice

Summary Experiments designed to investigate concomitant enhancement of tumor growth in the lungs of tumor-bearing mice are reported. When a fibrosarcoma (NFSA)³ that had arisen spontaneously in a C₃Hf/Bu mouse was transplanted into the hind legs of syngeneic mice 2 weeks prior to IV tumor challenge, the tumor-bearing mice developed more lung colonies than did normal controls. Paradoxically, the same mice demonstrated concomitant resistance to an IM tumor challenge. Animals bearing the tumor for only 1 week and those from which the tumor had been excised after 2 weeks' growth showed neither enhancement nor resistance to lung colony growth. Enhancement in mice bearing the tumor for 2 weeks was shown not to be due to metastases seeded from the primary tumor. Tumor-bearing animals receiving whole-body irradiation (WBI) 1 day before or 12 days after tumor transplantation showed no enhancement compared with nontumor-bearing WBI controls. Mice receiving partial body radiation with the thorax shielded also failed to show concomitant enhancement. Adult thymectomy alone did not affect the enhancement, while thymectomy followed by whole-body irradiation and bone marrow-cell reconstitution abolished it. Although apparently dependent upon relatively long-lived T cells, enhancement was not tumor-specific; mice bearing another fibrosarcoma (FSA), which does not cross react immunologically with NFSA, also showed enhancement when challenged IV with NFSA. Treatment of tumor-bearing mice with C. parvum prior to IV challenge prevented the enhancement phenomenon.Animals used in this study were maintained in facilities approved by the American Association for Accreditation of Laboratory Animal Care, and in accordance with current United States Department of Agriculture and Department of Health, Education, and Welfare, National Institutes of Health, regulations and standards.Abbreviations used here are: NFSA, spontaneously arisen fibrosarcoma; FSA, methylcholanthrene-induced fibrosarcoma; LCR, lung colony ratio (number of lung colonies in experimental group over those in control group); TG time, tumor growth time (the time required for a tumor to reach 500 mm³ after transplantation); TxRB mice, thymectomized whole body-radiated and bone marrow-reconstituted mice.