Repression of lymphatic metastasis by a second implant of the same tumor.

Previous work in the rat D-12 fibrosarcoma model has shown that the incidence of macroscopic metastasis, located primarily in regional lymph nodes, is markedly increased after surgical removal of a primary subcutaneous tumor implant, in all probability by facilitating the outgrowth of already established micrometastases. The present work shows that a second implant of live D-12 tumor cells into a remote site effectively represses the outgrowth of macroscopic metastases. For the manifestation of the repressive effect, both the time interval elapsing between surgery and reimplantation of tumor cells and the size of the inoculum appear critical. Implantation of heavily irradiated D-12 cells or the prolonged delivery of ascites fluid by osmotic mini-pumps had no such repressive effect on metastatic tumor growth. Corynebacterium parvum administered into the tumor-bearing limb a few days before its amputation, but not into a remote subcutaneous site, suppressed the outgrowth of macroscopic metastases. The occurrence and efficient operation of concomitant tumor resistance in the D-12 tumor model, in which metastasis is primarily via lymphatics and resistance appears to involve a substantial portion nonspecific reactivity, is further evidence for a basic role of tumor/tumor interrelations in determining the final outcome of the host/tumor interaction.