Markwalder R, Reubi J C
Division of Cell Biology and Experimental Cancer Research, Institute of Pathology, University of Berne, Switzerland.
Cancer Res. 1999 Mar 1;59(5):1152-9.
Bombesin-like peptides such as gastrin-releasing peptide (GRP) have been shown to play a role in cancer as autocrine growth factors that stimulate tumor growth through specific receptors. To search for potential clinical indications for GRP analogues, it is important to identify human tumor types expressing sufficient amounts of the respective receptors. In the present study, we have evaluated the expression of GRP receptors in human nonneoplastic and neoplastic prostate tissues using in vitro receptor autoradiography on tissue sections with 125I-Tyr4-bombesin as radio-ligand. GRP receptors were detected, often in high density, in 30 of 30 invasive prostatic carcinomas and also in 26 of 26 cases of prostatic intraepithelial proliferative lesions, corresponding mostly to prostatic intraepithelial neoplasias. Well-differentiated carcinomas had a higher receptor density than poorly differentiated ones. Bone metastases of androgen-independent prostate cancers were GRP receptor-positive in 4 of 7 cases. Conversely, GRP receptors were identified in only a few hyperplastic prostates and were localized in very low density in glandular tissue and, focally, in some stromal tissue. In all of the cases, the receptors corresponded to the GRP receptor subtype of bombesin receptors, having high affinity for GRP and bombesin and lower affinity for neuromedin B. These data demonstrate a massive GRP receptor overexpression in prostate tissues that are neoplastically transformed or, like prostatic intraepithelial neoplasias, are in the process of malignant transformation. GRP receptors may be markers for early molecular events in prostate carcinogenesis and useful in differentiating prostate hyperplasia from prostate neoplasia Such data may not only be of biological significance but may also provide a molecular basis for potential clinical applications such as GRP-receptor scintigraphy for early tumor diagnosis, radiotherapy with radiolabeled bombesin-like peptide analogues, and chemotherapy with cytotoxic bombesin analogues.
胃泌素释放肽（GRP）等蛙皮素样肽已被证明在癌症中作为自分泌生长因子，通过特定受体刺激肿瘤生长。为了寻找GRP类似物的潜在临床应用指征，识别表达足够量相应受体的人类肿瘤类型很重要。在本研究中，我们使用以125I-Tyr4-蛙皮素为放射性配体的体外受体放射自显影技术，评估了GRP受体在人类非肿瘤性和肿瘤性前列腺组织中的表达。在30例浸润性前列腺癌中的30例以及26例前列腺上皮内增殖性病变（大多对应前列腺上皮内瘤变）中的26例中均检测到GRP受体，且通常密度较高。高分化癌的受体密度高于低分化癌。雄激素非依赖性前列腺癌的骨转移灶在7例中有4例GRP受体呈阳性。相反，仅在少数增生性前列腺中发现GRP受体，且在腺组织中密度极低，仅在局部一些间质组织中有表达。在所有病例中，这些受体对应于蛙皮素受体的GRP受体亚型，对GRP和蛙皮素具有高亲和力，对神经降压素B具有较低亲和力。这些数据表明，在发生肿瘤转化的前列腺组织或如前列腺上皮内瘤变正在发生恶性转化的组织中，GRP受体大量过表达。GRP受体可能是前列腺癌发生早期分子事件的标志物，有助于区分前列腺增生和前列腺肿瘤。这些数据不仅可能具有生物学意义，还可能为潜在的临床应用提供分子基础，如用于早期肿瘤诊断的GRP受体闪烁显像、用放射性标记的蛙皮素样肽类似物进行放射治疗以及用细胞毒性蛙皮素类似物进行化疗。
