Reubi J C, Laissue J, Krenning E, Lamberts S W
Sandoz Research Institute Berne Ltd., Switzerland.
J Steroid Biochem Mol Biol. 1992 Sep;43(1-3):27-35. doi: 10.1016/0960-0760(92)90184-k.
Somatostatin receptors (SS-R) have been identified in membrane homogenates or tissue sections from several hundred tumors. SS-R were found in most neuroendocrine tumors, i.e. GH and TSH producing pituitary tumors, endocrine gastroenteropancreatic (GEP) tumors, paragangliomas, pheochromocytomas, medullary thyroid carcinomas (MTC) and small cell lung carcinomas. SS-R were also expressed in a majority of malignant lymphomas, in several brain tumors (all meningiomas, most astrocytomas) and in breast tumors. The majority of tumors expressing SS-R are rather differentiated (i.e. astrocytomas vs glioblastomas), but exceptions exist (high grade malignant lymphomas). An inverse relationship exists between SS-R and receptors for epidermal growth factor (EGF-R) incidence in lung tumors, glial tumors and most breast tumors, whereas meningiomas express simultaneously both receptors. A minority of tumors (ovarian tumors, MTC, insulinomas) express a subtype of SS-R, characterized by low affinity for the octapeptide SS analog octreotide. The function mediated by SS-R in human tumors may differ according to the tumor type. SS-R in pituitary and GEP tumor mediate hormone secretion inhibition with, in addition, possibly some antiproliferative effects. In meningiomas, however, activation of SS-R inhibits forskolin-stimulated adenylate cyclase activity, and weakly stimulates proliferation. Whereas SS-R seem to mediate antiproliferative effects in animal models and cell lines of lymphomas, breast and lung tumors, such an effect has not yet been convincingly documented in human primary tumors. The clinical implications of the presence of SS-R in tumors are manyfold: (1) as a predictive marker for efficient therapy with octreotide in pituitary and GEP tumors; (2) as a diagnostic marker: for pathobiochemical classification of tumors, using in vitro detection methods; for clinical evaluation using in vivo scanning techniques; (3) as a prognostic marker; and (4) as a potential radiotherapeutic target.
在数百种肿瘤的膜匀浆或组织切片中已鉴定出生长抑素受体（SS-R）。在大多数神经内分泌肿瘤中发现了SS-R，即产生生长激素（GH）和促甲状腺激素（TSH）的垂体肿瘤、内分泌胃肠胰腺（GEP）肿瘤、副神经节瘤、嗜铬细胞瘤、甲状腺髓样癌（MTC）和小细胞肺癌。在大多数恶性淋巴瘤、几种脑肿瘤（所有脑膜瘤、大多数星形细胞瘤）和乳腺肿瘤中也表达了SS-R。大多数表达SS-R的肿瘤分化程度较高（如星形细胞瘤与胶质母细胞瘤），但也有例外（高级别恶性淋巴瘤）。在肺肿瘤、神经胶质瘤和大多数乳腺肿瘤中，SS-R与表皮生长因子受体（EGF-R）的发生率呈负相关，而脑膜瘤同时表达这两种受体。少数肿瘤（卵巢肿瘤、MTC、胰岛素瘤）表达一种SS-R亚型，其对八肽SS类似物奥曲肽的亲和力较低。SS-R在人类肿瘤中介导的功能可能因肿瘤类型而异。垂体和GEP肿瘤中的SS-R介导激素分泌抑制，此外，可能还有一些抗增殖作用。然而，在脑膜瘤中，SS-R的激活会抑制福斯高林刺激的腺苷酸环化酶活性，并微弱地刺激增殖。虽然在淋巴瘤、乳腺和肺肿瘤的动物模型和细胞系中，SS-R似乎介导抗增殖作用，但在人类原发性肿瘤中尚未得到令人信服的证实。肿瘤中存在SS-R的临床意义是多方面的：（1）作为垂体和GEP肿瘤使用奥曲肽进行有效治疗的预测标志物；（2）作为诊断标志物：用于使用体外检测方法对肿瘤进行病理生化分类；用于使用体内扫描技术进行临床评估；（3）作为预后标志物；以及（4）作为潜在的放射治疗靶点。
