Gastrin-releasing peptide receptors in non-neoplastic and neoplastic human breast
Gastrin-releasing peptide receptors in non-neoplastic and neoplastic human breast
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DOI：
10.1016/s0002-9440(10)65525-3
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发表时间：
1999-12-01
影响因子：
6
通讯作者：
Reubi, JC
中科院分区：
文献类型：
--
作者：
Gugger, M;Reubi, JC
调节肽胃泌素释放肽（GRP）可能作为刺激生长因子在人类癌症中发挥作用。为了了解 GRP 在人类乳腺癌中的潜在作用，我们使用 [I-125]Tyr(4)-铃蟾肽和 [I-125]D_Tyr(6)、β Ala(11)、Phe(13)、 Nle(14)-铃蟾肽(6-14) 作为放射性配体。在 46 个浸润性导管癌中的 29 个、17 个原位导管癌中的 11 个、4 个浸润性小叶癌中的 1 个、2 个原位小叶癌中的 1 个、以及 1 个粘液癌和 1 个管状癌的肿瘤上皮乳腺细胞中检测到 GRP 受体，通常呈高密度。在 52 例浸润性癌病例中的 32 例和 19 例原位癌病例中的 12 例肿瘤组织样本中发现了异质 GRP 受体分布。表达GRP受体的原发癌的淋巴结转移（n = 33）均为阳性，而周围淋巴网状组织均为阴性。 GRP 受体也以高密度存在，但在所有可用乳腺组织样本 (n = 23) 的导管和小叶中分布不均。所有受体均对应于铃蟾肽受体的 GRP 受体亚型，对 GRP 具有高亲和力，铃蟾肽酸对神经调节肽 B 具有较低亲和力。所有表达 GRP 受体的组织均用两种放射性配体进行类似的鉴定。这些数据不仅描述了高比例的 GRP 受体阳性肿瘤性乳腺组织，而且首次描述了非肿瘤性人类乳腺组织中普遍存在的 GRP 受体表达。除了表明 GRP 在乳腺生理学中的作用之外，这些数据还代表了 GRP 类似物潜在临床应用（例如 GRP 受体闪烁扫描、放射治疗或化疗）的分子基础。
The regulatory peptide gastrin-releasing peptide (GRP) may play a role in human cancer as a stimulatory growth factor. To understand the potential role of GRP in human breast cancer, we have evaluated GRP receptor expression in human non-neoplastic and neoplastic breast tissues and in axillary lymph node metastases, using in vitro receptor autoradiography on tissue sections with [I-125]Tyr(4)-bombesin and with [I-125]D_Tyr(6), beta Ala(11), Phe(13), Nle(14)-bombesin(6-14) as radioligands. GRP receptors were detected, often in high density, in neoplastic epithelial mammary cells in 29 of 46 invasive ductal carcinomas, in 11 of 17 ductal carcinomas in situ, in 1 of 4 invasive lobular carcinomas, in 1 of 2 lobular carcinomas in situ, and in 1 mucinous and 1 tubular carcinoma. A heterogeneous GRP receptor distribution was found in the neoplastic tissue samples in 32 of 52 cases with invasive carcinoma and 12 of 19 cases with carcinoma:in situ. The lymph node metastases (n = 33) from those primary carcinomas expressing GRP receptors were all positive, whereas surrounding lymphoreticular tissue was negative. GRP receptors were also present in high density but with heterogeneous distribution in ducts and lobules from all available breast tissue samples (n = 23), All of the receptors corresponded to the GRP receptor subtype of bombesin receptors, having high affinity for GRP and bombesin acid lower affinity for neuromedin B. All tissues expressing GRP receptors were identified similarly with both radioligands. These data describe not only a high percentage of GRP receptor-positive neoplastic breast tissues but also for the first time a ubiquitous GRP receptor expression in nonneoplastic human breast tissue. Apart from suggesting a role of GRP in breast physiology, these data represent the molecular basis for potential clinical applications of GRP analogs such as GRP receptor scintigraphy, radiotherapy, or chemotherapy.