Control of Lung Metastasis Progression in Mice: Role of Growth Kinetics of 3LL Lewis Lung Carcinoma and Host Immune Reactivity2, 3

Abstract

Studies were made of the growth of metastases of the 3LL Lewis lung carcinoma in tumor-bearing and tumorexcised C57BLl6 mice after intrafootpad inoculation of different cell doses to the intact or immunosuppressed host. The total metastatic volume was higher in tumor-bearing mice given transplants of low doses of 3LL cells (3×10⁴-1×10⁵) than in mice receiving high doses of cells (1×10⁵×10⁸). The growth of postoperative lung metastases depends on the size of the removal of local tumors and the rate of their development. Surgical removal of small, medium, or large local tumors, respectively, resulted in the development of smaller, similar, or larger volumes of pulmonary metastases compared to the metastases in tumor-bearing mice not having surgery. Accelerated growth of postoperative metastases in mice inoculated with low doses of 3LL cells was observed following removal of the local tumors of more than 310 mm³. The same effect was observed on mice given transplants of high doses of 3LL cells only when the removed local tumors had reached a volume of more than 550 mm³. In immunologically suppressed tumor-bearing mice. acceleration of the metastatic growth in the lungs was observed independently of the inoculum size. Even in the immunosupressed mice, the growth of metastases was not optimal, and an additional stimulus for their growth was achieved following the removal of local tumors. This finding suggested that immunologic and nonimmunologic mechanisms were involved in the control of the metastatic growth of 3LL tumors in mice.