Metastatic behavior of a murine reticulum cell sarcoma exhibiting organ-specific growth

The metastatic properties of the M5076 tumor, a reticulum cell sarcoma of ovarian origin, were examined. This tumor metastasizes preferentially to the peritoneal viscera (liver, ovaries, spleen, and kidneys) regardless of the site or route of tumor cell injection. Subcutaneous tumor growth followed by direct invasion into the peritoneum resulted in extensive generalized peritoneal involvement. However, when tumor cells were injected in the dorsum, external ear, or footpad, fewer and primarily hepatic metastases developed. Hepatic, splenic, ovarian, and renal tumor colonies were formed after i.v. injection of tumor cells. Radiolabeled tumor cells were used to study the arrest, distribution, and survival of tumor cells injected i.v. These tumor cells were rapidly arrested in the lungs and were retained there for 3 to 4 days. They then slowly detached, recirculated, and were arrested in the liver, where they subsequently developed into tumor nodules. These results strongly support the “soil-seed” hypothesis of metastatic growth and demonstrate that long-term retention of tumor cells in an organ need not result in the formation of a clinically obvious tumor nodule.