ISOLATION AND CHARACTERIZATION OF MULTIPLE CELL-TYPES FROM A SINGLE HUMAN COLONIC-CARCINOMA - TUMORIGENICITY OF THESE CELL-TYPES IN A XENOGRAFT SYSTEM

The HCA-7 cell line was established from a moderately well differentia ted mucinous adenocarcinoma of the colon, which showed histological he terogeneity. This was reflected in the morphological heterogeneity in early passages of the HCA-7 cell line but diminished as the cells were passaged in vitro. Nine subpopulations were isolated from early passa ge cultures of the HCA-7 line and maintained as cell lines. Each subpo pulation demonstrated a unique set of stable biological characteristic s in vitro. When established in vivo, there was a wide variation in xe nograft generation time. The parent cell line gave rise to six distinc t xenograft patterns, two of which had been observed in the primary ca rcinoma. Individual subpopulations yielded characteristic tumours whic h were composed of between one and four organizational patterns. Xenog rafts differed in both the organization of cells and the cell differen tiation within the different patterns. Mucous cells were absent from s ome tumours while abundant in others. The subpopulations isolated from the HCA-7 cell line provide a new and extensive model system for stud ying the generation and maintenance of phenotypic heterogeneity in col orectal carcinoma.