The effects of single versus triple intravenous injections of B16 melanoma cells on the development of pulmonary tumors in mice.

During natural metastasis, cancer cells are released continuously into the bloodstream and arrested in target organs; the process is repetitive rather than a single event. In this communication, the effect of preceding on successive "pulses" of cancer cells is discussed in relation to the arrest, retention and tumor formation of B16 melanoma cells in the lungs of mice receiving 3 separate tail-vein injections at 2-hr intervals. When animals received the same total number of cells in either 1 or 3 injections, no significant differences were detected in the initial arrest and subsequent retention in the lungs. However, 15 days after injection, mice which had received 3 pulses of cancer cells were found to have fewer pulmonary tumors than those which had received a single pulse of cells. The results show that interactions between 2 successive waves of B16 melanoma cells and their host did not affect the initial arrest and "short-term" retention of a third wave of radiolabelled cells. However, the "longer-term" experiments on tumor formation show that preceding pulses of cancer cells resulted in the lungs becoming more hostile to a succeeding pulse than was the case in appropriate controls. The results indicate that the relative metastatic capacities of cancer cells arrested in microvascular beds during hematogenous metastasis could well be diminished by antecedent interactions of this type.