Fleischmann Achim, Waser Beatrice, Reubi Jean Claude
Division of Cell Biology and Experimental Cancer Research, Institute of Pathology, University of Bern, CH-3010 Bern, Switzerland.
Endocr Relat Cancer. 2009 Jun;16(2):623-33. doi: 10.1677/ERC-08-0316.
Tumoral gastrin-releasing peptide (GRP) receptors are potential targets for diagnosis and therapy using radiolabeled or cytotoxic GRP analogs. GRP-receptor overexpression has been detected in endocrine-related cancer cells and, more recently, also in the vascular bed of selected tumors. More information on vascular GRP-receptors in cancer is required to asses their potential for vascular targeting applications. Therefore, frequent human cancers (n = 368) were analyzed using in vitro GRP-receptor autoradiography on tissue sections with the (125)I-[Tyr(4)]-bombesin radioligand and/or the universal radioligand (125)I-[d-Tyr(6), beta-Ala(11), Phe(13), Nle(14)]-bombesin(6-14). GRP-receptor expressing vessels were evaluated in each tumor group for prevalence, quantity (vascular score), and GRP-receptor density. Prevalence of vascular GRP-receptors was variable, ranging from 12% (prostate cancer) to 92% (urinary tract cancer). Different tumor types within a given site had divergent prevalence of vascular GRP-receptors (e.g. lung: small cell cancer: 0%; adenocarcinoma: 59%; squamous carcinoma: 83%). Also the vascular score varied widely, with the highest score in urinary tract cancer (1.69), moderate scores in lung (0.91), colon (0.88), kidney (0.84), and biliary tract (0.69) cancers and low scores in breast (0.39) and prostate (0.14) cancers. Vascular GRP-receptors were expressed in the muscular vessel wall in moderate to high densities. Normal non-neoplastic control tissues from these organs lacked vascular GRP-receptors. In conclusion, tumoral vessels in all evaluated sites express GRP-receptors, suggesting a major biological function of GRP-receptors in neovasculature. Vascular GRP-receptor expression varies between the tumor types indicating tumor-specific mechanisms in their regulation. Urinary tract cancers express vascular GRP-receptors so abundantly, that they are promising candidates for vascular targeting applications.
肿瘤胃泌素释放肽（GRP）受体是使用放射性标记或细胞毒性GRP类似物进行诊断和治疗的潜在靶点。已在内分泌相关癌细胞中检测到GRP受体过表达，最近在某些肿瘤的血管床中也检测到。需要更多关于癌症中血管GRP受体的信息，以评估它们在血管靶向应用中的潜力。因此，使用(125)I-[Tyr(4)]-蛙皮素放射性配体和/或通用放射性配体(125)I-[d-Tyr(6),β-Ala(11),Phe(13),Nle(14)]-蛙皮素(6-14)对368例常见人类癌症组织切片进行体外GRP受体放射自显影分析。在每个肿瘤组中评估表达GRP受体的血管的患病率、数量（血管评分）和GRP受体密度。血管GRP受体的患病率各不相同，范围从12%（前列腺癌）到92%（泌尿系统癌）。给定部位内的不同肿瘤类型血管GRP受体的患病率也不同（例如肺：小细胞癌：0%；腺癌：59%；鳞状细胞癌：83%）。血管评分也有很大差异，泌尿系统癌得分最高（1.69），肺癌（0.91）、结肠癌（0.88）、肾癌（0.84）和胆管癌（0.69）得分中等，乳腺癌（0.39）和前列腺癌（0.14）得分较低。血管GRP受体在肌肉血管壁中呈中度至高密度表达。这些器官的正常非肿瘤对照组织缺乏血管GRP受体。总之，所有评估部位的肿瘤血管均表达GRP受体,表明GRP受体在新生血管中具有主要生物学功能。血管GRP受体表达在肿瘤类型之间存在差异，表明其调节存在肿瘤特异性机制。泌尿系统癌血管GRP受体表达非常丰富，是血管靶向应用的有希望的候选者。
