Increased resistance towards oxidative stress accompanies enhancement of metastatic potential obtained by repeated in vivo passage of colon carcinoma cells in syngeneic rats

The colon carcinoma cell line CC531 is metastatic to liver after splenic injection in syngeneic rats. After repeated in vivo passages, a subline was selected that produced liver metastases at a considerably higher rate than the original cell line. These cells were characterized by increased intracellular glutathione, proliferation and ability to restore glutathione after exposure to oxidative stress, thus indicating an elevated resistance to oxidative stress. Furthermore, the increased metastatic ability was also accompanied by increased proliferation rate, adhesion to extracellular matrix proteins and endothelial cells, and secretion of a 60 kD matrix metalloproteinase. When cultured in vitro for a prolonged time (more than 30 trypsinizations), the cells showed a reduced in vivo metastatic ability, reduced secretion of three metalloproteinases including the 60 kD proteinase, and reduced intracellular glutathione. These results indicate that metastatic ability can be influenced through several adaptive mechanisms, and that the cell's ability to resist oxidative stress and maintain intracellular glutathione are of central importance.