Isolation and characterization of multiple cell types from a single human colonic carcinoma: tumourigenicity of these cell types in a xenograft system.

The HCA-7 cell line was established from a moderately well differentiated mucinous adenocarcinoma of the colon, which showed histological heterogeneity. 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 passage cultures of the HCA-7 line and maintained as cell lines. Each subpopulation demonstrated a unique set of stable biological characteristics in vitro. When established in vivo, there was a wide variation in xenograft generation time. The parent cell line gave rise to six distinct xenograft patterns, two of which had been observed in the primary carcinoma. Individual subpopulations yielded characteristic tumours which were composed of between one and four organizational patterns. Xenografts differed in both the organization of cells and the cell differentiation within the different patterns. Mucous cells were absent from some tumours while abundant in others. The subpopulations isolated from the HCA-7 cell line provide a new and extensive model system for studying the generation and maintenance of phenotypic heterogeneity in colorectal carcinoma.