The influence of the microenvironment of liver-specific tumor cell colonization in a murine tumor model

Abstract

Malignant tumors often show an organ-specific metastatic spread. Some cells of the primary apparently bear an affinity for growing in the microenvironment of certain organs. After i.v. injection of myofibrosarcoma cells from the primary ER 15-P into the tail vein of male C57/Bl6J mice, metastases developed in various organs. A tumor cell line (ER 15-Me3) isolated from liver metastases of the primary was found to colonize preferentially to the liver. To find out whether the liver specificity of the tumor cell line ER 15-Me3 depended on the hepatic microenvironment, tumor cells from this line were transplanted i.m. into the thighs of mice once (ER 15-Me3 i.m.1) or 5 times (ER 15-Me3 i.m.5), and then injected into the tail vein of mice. A part of the 5-times passaged tumor cell line was also injected into the mesenteric vein (ER 15-Me3 i.m.5-Me1) prior to reinjection into the tail vein.

Results: After i.v. administration of tumor cells from the first i.m. passage of the tumor cell line (ER 15-Me3 i.m.1) into the tail vein, the liver-specific metastatic behavior of tumor cells remained stable. Following the i.v. injection of tumor cells from the 5th i.m. transplant generation of the tumor cell line (ER 15-Me3 i.m.5) into the tail vein, organ distribution was similar to that of the primary. After only 1 mesenteric vein passage of the 5-times i.m. transplanted line ER 15-Me3 i.m.5-Me1 followed by i.v. injection into the tail vein, did tumor cells regain their liver-specific colonizing potential. Thus, the liver-specific tumor cell line seems to contain a small number of other tumor cell populations from the unselected primary. In the muscle, these tumor cells have a growth advantage over the liver-specific cells, while the latter will grow better in the liver. This indicates that the microenvironment may be one important factor influencing the organ-specific metastatic pattern of tumor cells.