Differentiation of normal and cultured preneoplastic tracheal epithelial cells in rats: importance of epithelial mesenchymal interactions.

Changes in the dependence on mesenchymal tissues for survival and differentiation in inbred F344 female rats were investigated in tracheal epithelial cells exposed to 7, 12-dimethylbenz[a]anthracene (DMBA) and 12-O-tetradecanoylphorbol 13-acetate (TPA). Fresh suspensions of normal tracheal epithelium or cultured preneoplastic cells were inoculated into isolated organ segments (trachea, esophagus, bladder, or small intestine) or into Dacron containers that were then implanted subdermally into isogenic recipients. At various times after cell inoculation and implantation, tissues were removed for histologic evaluation. Normal cells inoculated into frozen-thawed trachea, esophagus, bladder, and intestine yielded a regular mucociliary epithelium. Normal cell inocula did not, however, survive in tracheae previously heated (100 degrees C), fixed in ethanol, or digested with collagenase; nor did normal cells survive in Dacron containers unless tracheal fibroblasts plus epithelial cells were inoculated together. DMBA- and TPA-exposed cell populations with increased growth capacity in vitro survived and differentiated on all of the above substrates. Our observations were consistent with those of other investigators in that normal cell survival and differentiation depend to some extent on interaction with extracellular material(s) present in various organs. The essential elements were not supplied by subdermal fibroblasts alone. For survival and differentiation in vivo, preneoplastic cells appeared to have less stringent substrate requirements than did normal cells. Application of the described techniques to the study of changes occurring early in the development of neoplastic disease is discussed.