DEVELOPMENT AND CHARACTERIZATION OF NORMAL COLONIC EPITHELIAL-CELL LINES DERIVED FROM NORMAL MUCOSA OF PATIENTS WITH COLON-CANCER

BACKGROUND: Researchers have tried for at least 20 years to develop a normal human colonic cell line suitable for in vitro studies of human colonic diseases. We report a breakthrough development of two normal c olon-derived cell lines. They are designated NCM356 and NCM425. MATERI ALS AND METHODS: Tile cells were collected from the histologically nor mal colonic margin of patients undergoing resection for colon adenocar cinomas and grown in culture. RESULTS: Since NCM356 and NCM425 have no w been subcultured 22 and 19 times, each has undergone more than 40 po pulation doublings. Neither cell line has shown evidence of terminal d ifferentiation. Immunohistochemical characterization studies demonstra ted that they are epithelial cells. They variably expressed subsets of other markers, including tumor markers, but did not grow in soft agar . NCM356 did not form tumors, whereas NCM425 was tumorigenic in immuno deficient mice. CONCLUSION: These two cell lines represent the first s uccessful in vitro culture of hunan colonocytes derived from normal mu cosa. NCM356 is closer to normal, but seems to represent an early stag e of cell transformation, possibly correlated with immortalization. In contrast, in vitro culture of the NCM425 cell line appears to have se lected for later progression to malignancy. These lines are important resources for studying colon cancer and the physiology of intestinal c ells.