Early tumor growth in metastatic organs influenced by the microenvironmentis an important factor which provides organ specificity of colon cancer metastasis

We have previously demonstrated that liver metastases in nude mice and lung metastases in nude rats occurred specifically, when KM12SM human colon car cinoma cells were inoculated orthotopically into the cecal wall of nude mic e and rats. To clarify the relationship between the tumor growth potential in the metastatic organs and the metastatic organ preference in these two m etastatic models, we have evaluated the in vitro cell growth activities aff ected by the organ conditioned medium (CM) from the liver and lung, and the in vivo growth activities of the ectopic implanted tumors in the liver and lung. The tumorigenicity of the ectopic implanted tumors was 100% in mouse liver, 33% in rat liver, 50% in mouse lung, and 75% in rat lung. The crude liver CM of the animals showed inhibitory activities for KM12SM cell growt h in a dosage-dependent manner, and the crude lung CM stimulated KM12SM cel l growth. The liver CM of nude mice inhibited the KM12SM cell growth more s trongly compared with the CM of nude rats, and the lung CM of nude rats was more strongly stimulated compared with the CR I of nude mice. The liver CM of nude mice had non-heparin binding factors, which stimulated or inhibite d KM12SM cell growth, in a molecular weight range of 50 to 100 kDa. By cont rast, the liver CM of nude rats showed no growth stimulating activity for K M12SM cells. These results suggest that the metastatic organ specificity of KM12SM cells may depend on the early tumor growth influenced by the microe nvironment in metastatic organs.