High expression of gastrin-releasing peptide receptors in the vascular bed of urinary tract cancers: promising candidates for vascular targeting applications
High expression of gastrin-releasing peptide receptors in the vascular bed of urinary tract cancers: promising candidates for vascular targeting applications
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DOI：
10.1677/erc-08-0316
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发表时间：
2009-06-01
影响因子：
3.9
通讯作者：
Reubi, Jean Claude
中科院分区：
文献类型：
--
作者：
Fleischmann, Achim;Waser, Beatrice;Reubi, Jean Claude
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。在内分泌相关的癌细胞中检测到GRP受体过表达，最近在选定肿瘤的血管床中也检测到GRP受体过表达。因此，使用I-125-[Tyr（4）]-蛙皮素放射性配体和/或通用放射性配体I-125-[D-Tyr（6），β-Ala（11），Phe（13），Nle（14）]-蛙皮素（6-14）。在每个肿瘤组中评估GRP受体表达血管的患病率、数量（血管评分）和GRP受体密度。血管GRP受体的患病率是可变的，范围从12%（前列腺癌）到92%（尿路癌）。给定部位内的不同肿瘤类型具有不同的血管GRP受体流行率（例如，肺：小细胞癌：0%，腺癌。鳞状细胞癌：83%）。此外，血管评分差异很大，尿路癌评分最高（1.69），肺癌（0.91）、结肠癌（0.88）、肾癌（0.84）和胆道癌（0.69）评分中等，乳腺癌（0.39）和前列腺癌（0.14）评分较低。血管GRP受体在肌肉血管壁中以中等至高密度表达。来自这些器官的正常非肿瘤对照组织缺乏血管GRP受体。总之，所有评价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重要的生物学功能。血管GRP受体表达在肿瘤类型之间变化，表明其调节中的肿瘤特异性机制。尿路癌表达血管GRP受体如此丰富，以至于它们是血管靶向应用的有希望的候选者。与内分泌有关的癌症（2009年）16 623-633
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 G R P-receptor autoradiography on tissue sections with the I-125-[Tyr(4)]-bombesin radioligand and/or the universal radioligand I-125-[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. Endocrine-Related Cancer (2009) 16 623-633