Drucker D J, Asa S L, Silverberg J, Brubaker P L
Department of Medicine, Toronto General Hospital, Ontario, Canada.
Cancer. 1990 Apr 15;65(8):1762-70. doi: 10.1002/1097-0142(19900415)65:8<1762::aid-cncr2820650817>3.0.co;2-q.
Endocrine tumors of the pancreas may produce characteristic syndromes attributable to the increased secretion of one or more hormones. These tumors provide valuable opportunities for the analysis of hormone biosynthesis and secretion in the neoplastic human endocrine cell. The authors studied a pancreatic endocrine tumor obtained from a patient with classical glucagonoma syndrome. Characterization of plasma and tumor glucagon-like immunoreactivity (GLI) by high-performance liquid chromatography and radioimmunoassay for GLI showed different chromatographic profiles, with glucagon the major molecular form in the tumor, and glicentin and oxyntomodulin predominating in plasma. Although immunocytochemical staining of the tumor showed only focal weak positivity for glucagon, tumor extracts contained large amounts of immunoreactive GLI peptide. Northern blot analysis of tumor RNA demonstrated that abundant glucagon mRNA transcripts were present, just slightly larger in size than those detected in normal pancreas and intestine. Electron microscopic analysis of the tumor cellular ultrastructure revealed only occasional small electron dense secretory granules. A large number of complex lysosome-like structures of variable size and electron density were detected throughout the cytoplasm and ringing the nucleus of most cells, a feature atypical of endocrine tumors of the pancreas. Primary cultures of dispersed tumor cells were established and, in contrast to previous results, were obtained using normal or neoplastic islet cell models, GLI secretion was found to be stimulated eightfold by incubation with 5 mM dibutyryl cyclic adenosine monophosphate. Phorbol myristate acetate, the calcium ionophore A23187, and sodium butyrate had no effect on GLI secretion in vitro. These observations indicate that neoplastic human A cells may have abnormalities at different points in the biosynthesis and secretion of glucagon.
胰腺内分泌肿瘤可能会产生一些特征性综合征，这归因于一种或多种激素分泌增加。这些肿瘤为分析肿瘤性人类内分泌细胞中的激素生物合成和分泌提供了宝贵的机会。作者研究了一名患有典型胰高血糖素瘤综合征患者的胰腺内分泌肿瘤。通过高效液相色谱法和胰高血糖素样免疫反应性（GLI）放射免疫分析法对血浆和肿瘤中的GLI进行表征，结果显示出不同的色谱图谱，肿瘤中的主要分子形式是胰高血糖素，而血浆中则以甘丙胰高血糖素和胃泌酸调节素为主。尽管肿瘤的免疫细胞化学染色仅显示胰高血糖素呈局灶性弱阳性，但肿瘤提取物中含有大量免疫反应性GLI肽。对肿瘤RNA进行Northern印迹分析表明，存在大量的胰高血糖素mRNA转录本，其大小仅略大于在正常胰腺和肠道中检测到的转录本。对肿瘤细胞超微结构的电子显微镜分析仅偶尔发现小的电子致密分泌颗粒。在大多数细胞的整个细胞质中以及围绕细胞核检测到大量大小和电子密度各异的复杂溶酶体样结构，这是胰腺内分泌肿瘤的非典型特征。建立了分散肿瘤细胞的原代培养物，与先前的结果相反，此次是使用正常或肿瘤性胰岛细胞模型获得的，发现用5 mM二丁酰环磷酸腺苷孵育可使GLI分泌增加八倍。佛波酯肉豆蔻酸酯、钙离子载体A23187和丁酸钠在体外对GLI分泌没有影响。这些观察结果表明，肿瘤性人类A细胞在胰高血糖素的生物合成和分泌的不同点可能存在异常。
