Wang F, Larsson J, Adrian T E, Gasslander T, Permert J
Department of Surgery, Karolinska Institute at Huddinge University Hospital, Huddinge, S-14186, Sweden.
J Surg Res. 1998 Sep;79(1):13-9. doi: 10.1006/jsre.1998.5393.
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.
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.
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).
Pancreatic islets regulate both growth and glucose metabolism of adjacent exocrine cancer cells. beta-cell-derived insulin may be one of the factors inducing these effects. Insulin release from islet beta-cells is compromised in the presence of exocrine cancer cells.
已发现外分泌性胰腺腺癌与胰岛之间存在相互作用。胰腺腺癌细胞的生长可受胰岛素和生长抑素等胰岛激素调节。相反，内分泌胰腺功能障碍常伴随外分泌恶性肿瘤。这些相互作用的潜在机制尚未明确。
将人胰腺腺癌细胞（HPAF细胞）与分离的大鼠胰岛在双室孔中共同培养。在单独孔中培养的HPAF细胞和胰岛作为对照。在单独实验中，将HPAF细胞与两种浓度的外源性胰岛素孵育，其中一种浓度反映了共同培养实验中所见的胰岛素分泌水平。
与胰岛共同孵育2天或5天后，HPAF细胞的增殖增加了约50%（P<0.05）。HPAF细胞与胰岛共同培养导致培养基中葡萄糖浓度降低幅度更大（P<0.01），乳酸积累增加（P<0.05）。共同培养孵育的前2至3天，培养基中的胰岛素浓度显著降低（P<0.05）。相比之下，对照胰岛的胰岛素分泌直到实验第5天才显著降低。两种浓度的外源性胰岛素均刺激了HPAF细胞的生长（P<0.05）。胰岛素刺激的HPAF细胞还表现出葡萄糖消耗和乳酸生成增加（P<0.05）。
胰岛调节相邻外分泌癌细胞的生长和葡萄糖代谢。β细胞来源的胰岛素可能是诱导这些效应的因素之一。在外分泌癌细胞存在的情况下，胰岛β细胞的胰岛素释放受损。
