Endocrine differentiation by a human rectal adenocarcinoma cell line (HRA-19)

Colorectal epithelium is composed of a variety of cell types, including absorptive, mucous and endocrine cells. All of these cell types are thought to arise from stem cells located at the base of the crypt. However, the factors which control these differentiation pathways are poorly understood. In attempts to establish differentiated in vitro systems, one approach has been to grow primary human colorectal adenocarcinomas as cell lines. Some of these cell lines retain a sufficient number of the differentiated features of their tissue of origin to make them useful experimental systems for studying differentiation. This study describes the characterisation of such a cell line, the HRA-19 line. HRA-19 cells were derived from a primary human rectal adenocarcinoma. The cells grew as monolayers in vitro on tissue-culture plastic and remained pleomorphic even after 150 passages in vitro. Some colonies of cells expressed alkaline phosphatase activity, an enzyme normally expressed in vivo by absorptive cells of the upper crypt and surface epithelium. No evidence of differentiation into goblet or endocrine cells was obtained in monolayer cultures of HRA-19 cells. Xenografts of this cell line contained cells with the ultrastructural characteristics of absorptive and endocrine cells. These endocrine cells exhibited Grimelius silver staining, displayed formaldehyde-induced fluorescence and contained many basally located, electron-dense granules. When grown as monolayers, clones of this cell line retained the heterogeneity with respect to morphology and alkaline phosphatase expression of the parent cell line. It is proposed that this cell line is derived from malignant progenitor cells which retain the ability to differentiate.(ABSTRACT TRUNCATED AT 250 WORDS)