Reubi J C, Waser B, Laissue J A, Gebbers J O
Division of Cell Biology, Institute of Pathology, University of Berne, Switzerland.
Cancer Res. 1996 Apr 15;56(8):1922-31.
Somatostatin and vasoactive intestinal peptide (VIP) have been shown to be of diagnostic and therapeutic interest in several types of human epithelial tumors expressing the respective receptor. The present study evaluates the presence of somatostatin and VIP receptors in 64 primary or metastatic human mesenchymal tumors. In vitro receptor autoradiography on cryostat sections was performed using 125I-labeled [Tyr3]-octreotide as well as 125I-labeled [Leu8,D-Trp22,Try25]-somatostatin-28 as radioligands for somatostatin receptors and 125I-labeled VIP as radioligand for VIP receptors. Somatostatin receptors were identified in bone and vascular/perivascular tumors (3 of 3 osteosarcomas, 1 of 1 giant cell tumor, 2 of 2 angiosarcomas, and 4 of 4 hemangiopericytomas), in 2 of 2 synovial sarcomas, in 2 of 5 histiocytomas, and in several muscle cell tumors (1 of 2 leiomyomas, 2 of 4 leiomyosarcomas, and 3 of 5 rhabdomyosarcomas) but were absent in 4 liposarcomas, 3 mesotheliomas, 3 chondrosarcomas, 10 Ewing sarcomas, 11 schwannomas, and 5 Wilms' tumors. VIP receptors were identified in 3 of 3 differentiated liposarcomas, 2 of 2 angiosarcomas, 4 of 4 hemangiopericytomas, 2 of 2 synovial sarcomas, 3 of 3 mesotheliomas, 5 of 5 Wilms tumors, as well as in 2 of 5 histiocytomas, 1 of 2 leiomyomas, 2 of 4 leiomyosarcomas, 3 of 3 intermediately differentiated rhabdomyosarcomas, and 1 of 3 osteosarcomas but not in chondrosarcomas, Ewing sarcomas, schwannomas, or undifferentiated rhabdomyosarcomas. The receptors were located on neoplastic cells. The somatostatin receptors were of high affinity and of high specificity for biologically active somatostatin analogues with high affinity for somatostatin-14 and somatostatin-28 as well as for octreotide, thus representing the sst2 subtype; in a few cases of tumors having somatostatin receptors with low affinity for octreotide, in situ hybridization techniques identified preferentially sst1 mRNA. These data suggest that human mesenchymal tumors may be targets for somatostatin and/or VIP receptor in vivo imaging; they may also be potential targets for somatostatin or VIP analogue therapy.
生长抑素和血管活性肠肽（VIP）已被证明在表达相应受体的几种人类上皮性肿瘤中具有诊断和治疗意义。本研究评估了64例原发性或转移性人类间叶组织肿瘤中生长抑素和VIP受体的存在情况。使用125I标记的[酪氨酸3]-奥曲肽以及125I标记的[亮氨酸8，D-色氨酸22，酪氨酸25]-生长抑素-28作为生长抑素受体的放射性配体，125I标记的VIP作为VIP受体的放射性配体，对冰冻切片进行体外受体放射自显影。在骨肿瘤和血管/血管周围肿瘤（3例骨肉瘤中的3例、1例巨细胞瘤中的1例、2例血管肉瘤中的2例、4例血管外皮细胞瘤中的4例）、2例滑膜肉瘤中的2例、5例组织细胞瘤中的2例以及几种肌肉细胞瘤（2例平滑肌瘤中的1例、4例平滑肌肉瘤中的2例、5例横纹肌肉瘤中的3例）中鉴定出了生长抑素受体，但在4例脂肪肉瘤、3例间皮瘤、3例软骨肉瘤、10例尤因肉瘤、11例神经鞘瘤和5例肾母细胞瘤中未发现。在3例分化型脂肪肉瘤中的3例、2例血管肉瘤中的2例、4例血管外皮细胞瘤中的4例、2例滑膜肉瘤中的2例、3例间皮瘤中的3例、5例肾母细胞瘤中的5例以及5例组织细胞瘤中的2例、2例平滑肌瘤中的1例、4例平滑肌肉瘤中的2例、3例中间分化型横纹肌肉瘤中的3例、3例骨肉瘤中的1例中鉴定出了VIP受体，但在软骨肉瘤、尤因肉瘤、神经鞘瘤或未分化型横纹肌肉瘤中未发现。这些受体位于肿瘤细胞上。生长抑素受体对生物活性生长抑素类似物具有高亲和力和高特异性，对生长抑素-14、生长抑素-28以及奥曲肽具有高亲和力，因此代表sst2亚型；在少数对奥曲肽亲和力低的生长抑素受体肿瘤病例中，原位杂交技术优先鉴定出sst1 mRNA。这些数据表明，人类间叶组织肿瘤可能是生长抑素和/或VIP受体体内成像的靶点；它们也可能是生长抑素或VIP类似物治疗的潜在靶点。
