Feindt J, Becker I, Blömer U, Hugo H H, Mehdorn H M, Krisch B, Mentlein R
Anatomisches Institute, Universität Kiel, Germany.
J Neurochem. 1995 Nov;65(5):1997-2005. doi: 10.1046/j.1471-4159.1995.65051997.x.
Expression of receptors for the neuropeptide somatostatin was investigated in vitro in rat and human astrocytes, glioma cell lines, and solid human glial tumors that were all immunopositive for the astrocytic marker glial fibrillary acidic protein. After affinity labelling with a peptide-gold conjugate of known biological activity, somatostatin-binding sites could be visualized at the light-and electron-microscopic level on the surface of glial cells. Glioma cells were generally labeled more strongly than were normal astrocytes and preferentially bound the ligand at their processes and not at their somata as were normal cells. Somatostatin transmembrane receptor (SSTR) subtype expression was probed by reverse transcription-polymerase chain reaction: In rat and human cortical astrocytes and in one glioma cell line (U 118), a pattern of three subtypes (SSTR-1, SSTR-2, and SSTR-4) was detected, whereas, in all other glioma cell lines and in six solid glial tumors investigated, the SSTR-2 subtype was relatively stronger, expressed either alone or in combination with SSTR-1; sometimes SSTR-3 or SSTR-4 was demonstrated in clearly reduced amounts. In astrocytes and gliomas, somatostatin reduced the levels of cyclic AMP elicited by the adenylate cyclase activator forskolin indicating that at least one of the receptor subtypes is negatively linked to adenylate cyclase. In contrast to other cell types, somatostatin did not inhibit the basal or the fetal calf serum-stimulated proliferation of astrocytes, glioma cell lines, or glial tumors in culture. Thus, strong SSTR-2 subtype expression characterizes glial tumors, but somatostatin is ineffective in inhibiting their growth.
在大鼠和人类星形胶质细胞、胶质瘤细胞系以及实体性人类胶质肿瘤中对神经肽生长抑素受体的表达进行了体外研究，这些细胞和肿瘤均对星形胶质细胞标志物胶质纤维酸性蛋白呈免疫阳性。在用具有已知生物活性的肽 - 金偶联物进行亲和标记后，在光镜和电镜水平上均可在胶质细胞表面观察到生长抑素结合位点。胶质瘤细胞通常比正常星形胶质细胞标记更强，并且与正常细胞不同，它们优先在其突起而非胞体结合配体。通过逆转录 - 聚合酶链反应检测生长抑素跨膜受体（SSTR）亚型表达：在大鼠和人类皮质星形胶质细胞以及一种胶质瘤细胞系（U 118）中，检测到三种亚型（SSTR - 1、SSTR - 2和SSTR - 4）的表达模式，而在所有其他胶质瘤细胞系以及所研究的六个实体性胶质肿瘤中，SSTR - 2亚型相对更强，单独表达或与SSTR - 1联合表达；有时SSTR - 3或SSTR - 4的表达量明显降低。在星形胶质细胞和胶质瘤中，生长抑素降低了由腺苷酸环化酶激活剂福斯高林引起的环磷酸腺苷水平，表明至少一种受体亚型与腺苷酸环化酶呈负相关。与其他细胞类型不同，生长抑素并未抑制培养的星形胶质细胞、胶质瘤细胞系或胶质肿瘤的基础增殖或胎牛血清刺激的增殖。因此，强烈的SSTR - 2亚型表达是胶质肿瘤的特征，但生长抑素在抑制其生长方面无效。
