IN-VITRO INFLUENCES BETWEEN PANCREATIC ADENOCARCINOMA CELLS AND PANCREATIC-ISLETS

Background Interactions have been found between exocrine pancreatic ad enocarcinoma and islets of Langerhans. Growth of pancreatic adenocarci noma cells can be regulated by islet hormones such as insulin and soma tostatin. Conversely, dysfunction of endocrine pancreas frequently acc ompanies the exocrine malignancy. The mechanisms underlying these inte ractions have not been defined. Materials and methods. Human pancreati c adenocarcinoma cells (HPAF cells) were cocultured with isolated rat pancreatic islets in two-compartment wells. HPAF cells and islets cult ured in separate wells served as controls. In separate experiments, HP AF cells were incubated with two concentrations of exogenous insulin, including one reflecting the levels of insulin secretion seen in the c oculture experiments. Results. Proliferation of HPAF cells was increas ed by about 50% following a 2- or 5-day incubation with pancreatic isl ets (P < 0.05). Coculture of HPAF cells and pancreatic islets was asso ciated with a greater reduction in glucose concentrations (P < 0.01) a nd an increase in lactate accumulation (P < 0.05) in the culture media . Insulin concentrations in the media were significantly decreased dur ing the first 2-3 days of the coculture incubation (P < 0.05). In cont rast, insulin secretion from control islets was not significantly decr eased until the fifth day of the experiment. The growth of HPAF cells was stimulated by both concentrations of exogenous insulin (P < 0.05). The insulin-stimulated HPAF cells also showed an enhanced glucose con sumption and lactate production (P < 0.05). Conclusions. Pancreatic is lets regulate both growth and glucose metabolism of adjacent exocrine cancer cells, beta-cell-derived insulin may be one of the factors indu cing these effects. Insulin release from islet beta-cells is compromis ed in the presence of exocrine cancer cells. (C) 1998 Academic Press.