Selective metastasis of a transplantable reticulum cell sarcoma

A transplantable reticulum cell sarcoma, type B, (RCS) which developed spontaneously in a C3Hf mouse, and consistently metastasizes to the spleen was investigated for the purpose of explaining the mechanics of preferential metastasis. Dose-effect studies of the RCS were performed in C3Hf/Pi and (C3Hf x BALB/c) F1 hybrid mice. It was determined that the median survival time of the mice was inversely proportional to the concentration of circulating tumor cells, and that approximately 170 RCS cells were required to induce tumors which would kill 50% of the animals in 30 days. The tumor appeared to develop initially in the splenic red pulp and spread to other organs as the number of RCS cells in the circulation increased. An estimate of the tumor's growth rate in vivo showed the neoplasm's mean generation time to increase cubically with time. Splenectomized mice had a better rate of survival than the sham-operated controls injected intraperitoneally with the same concentration of RCS cells, suggesting that a suitable environment for the early establishment and protection of the neoplasm was probably provided by the spleen. The fate of the RCS and its dissemination in a syngeneic host was examined with an intracellular radioactive label, 1^5iodo-deoxy-uridine (125lUdR). The label had little effect on the biological behavior of the RCS cell. Approximately 90%> of the label's activity was associated with the DNA fraction of the cell. When the RCS cells died almost all of the125i was excreted, thus providing a means for q_uantitating cell loss. Mice were injected intravenously, intraperitoneally and sub-cutaneously with viable and non-viable 125iUdR labelled RCS cells. Anywhere from 60% to 82% (depending on route of injection) of the RCS cells were destroyed within 2h hours post injection. The cell destruction could not he attributable to a specific-immune response. The organs of mice injected intravenously with labelled RCS cells were assayed for the number of tumor cells arrested. An influx of RCS cells in the spleen was observed, while the other organs examined demonstrated a continuous decrease in tumor cells arrested, indicating that the RCS cells were either being arrested and destroyed by the organs or were not being arrested and subsequently destroyed elsewhere. The results of these experiments allow the following conclusions. The RCS has a high degree of transplantability"" with a preference for splenic tissue, subject to its concentration in the circulation. The spleen provides a protective environment suitable for the growth of the neoplasm, since circulating RCS cells not arrested by the spleen are subject to destruction elsewhere. The phenomenon of the RCS's preferential metastasis may be explained on the basis of the specialized growth characteristics of the tumor cell and the organ it is arrested by.""