Selection of liver-colonizing tumor cells from a murine fibrosarcoma induced by methylcholanthrene

Summary

An experimental tumor model was developed to study the organ preference of malignant tumors. The primary tumor ER 15-P was induced by in-oculation of 1 mg methylcholanthrene in 0.1 ml sesame oil into the left femoral muscle of a female C57/B1₆J mouse. The tumor was palpable 100 days after induction. Spontaneous lung metastases were found at autopsy on day 128. Serial IM transplantation of tumor cells from the primary ER 15-P resulted in pulmonary metastases in all male and female mice. After IV injection of tumor cells from ER 15-P to male mice, colonies were found in lungs, thoracic cavity, liver, kidneys and occasionally also adrenals; female mice sometimes had ovarian metastases in addition, but no hepatic metastases. Liver-colonizing tumor cells were selected in male mice as follows: (a) IV injection of tumor cells from primary ER 15-P; (b) removal of tumor cells from liver tumor nodules, reinjection into mesenteric vein; (c) preparation of resulting tumors in the liver, reinjection of these cells through the portal system in one group of mice, and IV administration into tail vein in another group: (d) IM inoculation of tumor cells of the mesenteric passage in the left gastrocnemius muscle of mice prior to IV injection via tail vein in another group. Steps c and d were repeated three times. The procedure resulted in a highly significant decrease of tumor cell colonization to lungs and other organs, and a preferential increase of liver colonization. The liver preference of cell lines thus selected was obvious. Possible mechanisms for the organ preference of malignant tumors are discussed.