In VitroInfluences between Pancreatic Adenocarcinoma Cells and Pancreatic Islets

Abstract

Background.Interactions have been found between exocrine pancreatic adenocarcinoma and islets of Langerhans. Growth of pancreatic adenocarcinoma cells can be regulated by islet hormones such as insulin and somatostatin. Conversely, dysfunction of endocrine pancreas frequently accompanies the exocrine malignancy. The mechanisms underlying these interactions have not been defined.Materials and methods.Human pancreatic adenocarcinoma cells (HPAF cells) were cocultured with isolated rat pancreatic islets in two-compartment wells. HPAF cells and islets cultured in separate wells served as controls. In separate experiments, HPAF cells were incubated with two concentrations of exogenous insulin, including one reflecting the levels of insulin secretion seen in the coculture experiments.Results.Proliferation of HPAF cells was increased by about 50% following a 2- or 5-day incubation with pancreatic islets (P< 0.05). Coculture of HPAF cells and pancreatic islets was associated with a greater reduction in glucose concentrations (P< 0.01) and an increase in lactate accumulation (P< 0.05) in the culture media. Insulin concentrations in the media were significantly decreased during the first 2–3 days of the coculture incubation (P< 0.05). In contrast, insulin secretion from control islets was not significantly decreased 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 consumption and lactate production (P< 0.05).Conclusions.Pancreatic islets regulate both growth and glucose metabolism of adjacent exocrine cancer cells. β-cell-derived insulin may be one of the factors inducing these effects. Insulin release from islet β-cells is compromised in the presence of exocrine cancer cells.