Hennig I M, Laissue J A, Horisberger U, Reubi J C
Division of Cell Biology and Experimental Cancer Research, University of Berne, Switzerland.
Int J Cancer. 1995 Jun 9;61(6):786-92. doi: 10.1002/ijc.2910610608.
Primary human neoplasms were examined for the presence of substance-P receptors by receptor autoradiography with 125I-labelled Bolton-Hunter substance P. Substance-P receptors were localized and characterized in the neoplastic cells of 9/12 astrocytomas, 10/10 glioblastomas, 10/12 medullary thyroid carcinomas, 8/16 breast carcinomas and 4/5 ganglioneuroblastomas. Conversely, substance-P receptors were not or only rarely identified on non-small-cell carcinomas of the lung (1/16), neuroblastomas (0/8), adenocarcinomas of the colon (1/21) or the pancreas (1/9), or on malignant lymphomas (3/18). However, in the great majority of the investigated tumours, substance-P receptors were found on intra- and peritumoral blood vessels. All substance-P receptors detected had the pharmacological characteristics of the neurokinin-I receptor sub-type. In addition, the expression of somatostatin receptors was examined in all the neoplastic tissues mentioned above. Both substance-P and somatostatin receptors were present in astrocytomas and in ganglioneuroblastomas, whereas little or no receptor was found in pancreatic and non-small-cell lung carcinomas. The extent of somatostatin-receptor expression was inversely correlated to that of the substance-P receptors in glioblastomas, neuroblastomas and non-Hodgkin's lymphomas. The tumoral and vascular localization of substance-P receptors in tumours may have clinical implications. The use of radiolabelled substance P for in vivo scintigraphy may supplement the current set of diagnostic tools. Substance-P antagonists might be used in the treatment of tumours, as their binding to vascular receptors may decrease tumoral blood supply and drainage.
采用¹²⁵I标记的博尔顿-亨特P物质,通过受体放射自显影术检测原发性人类肿瘤中P物质受体的存在情况。在12例星形细胞瘤中的9例、10例胶质母细胞瘤、12例甲状腺髓样癌中的10例、16例乳腺癌中的8例以及5例神经节神经母细胞瘤中的4例的肿瘤细胞中定位并鉴定出了P物质受体。相反,在肺非小细胞癌(16例中的1例)、神经母细胞瘤(8例中的0例)、结肠腺癌(21例中的1例)或胰腺腺癌(9例中的1例)或恶性淋巴瘤(18例中的3例)中未发现或仅很少发现P物质受体。然而,在绝大多数被研究的肿瘤中,在肿瘤内和肿瘤周围血管上发现了P物质受体。所有检测到的P物质受体都具有神经激肽-1受体亚型的药理学特征。此外,还检测了上述所有肿瘤组织中生长抑素受体的表达情况。P物质和生长抑素受体在星形细胞瘤和神经节神经母细胞瘤中均有存在,而在胰腺和肺非小细胞癌中发现的受体很少或没有。在胶质母细胞瘤、神经母细胞瘤和非霍奇金淋巴瘤中,生长抑素受体的表达程度与P物质受体的表达程度呈负相关。肿瘤中P物质受体的肿瘤和血管定位可能具有临床意义。使用放射性标记的P物质进行体内闪烁扫描可能会补充现有的诊断工具。P物质拮抗剂可能用于肿瘤治疗,因为它们与血管受体的结合可能会减少肿瘤的血液供应和引流。