Differentiation of the human pancreatic adenocarcinoma cell line (Capan-1) in culture and co-culture with fibroblasts dome formation

This study was designed to investigate differentiation of human pancreatic duct carcinoma cells (Capan-I) in vitro. Observations on live cells, and electron microscopic examination, together with enzymological and immunocytochemical methods, have demonstrated that these cells differentiate spontaneously at an early stage. The cells are seen to be joined by apical junctions. High ATPase activity can be detected in the basolateral membranes, and the cells secrete a gastric type mucin (MI) bearing acidic groups. During differentiation in culture, they form domes which are thought to be the morphological expression of trans-epithelial transport of water and electrolytes. This particular structure is transitory, since after 6 days in culture all the cells lose their adhesivity, and form into floating cords. Co-culture of Capan-I cells and human, nude mice or chick embryo fibroblasts leads to a higher degree of differentiation of epithelial cells, reflected by the earlier appearance of numerous domes. In addition, the anchorage of Capan-I cells to fibroblasts prevents retraction of the monolayer, and enables the domes to be maintained in the cultures for more than one month. These findings suggest that Capan-I cells are able to carry out trans-epithelial movement of water and electrolytes. It is suggested that excretion of ions (bicarbonate and/or chloride) is preserved after transformation of pancreatic duct cells. Mucins (MI) and the recently described VIP receptor sites are also thought to play a part in these exchange processes.