Rauch I, Kofler Barbara
Department of Pediatrics, SALK and Paracelsus Medical University, Müllner Hauptstrasse 48, 5020 Salzburg, Austria.
Exp Suppl. 2010;102:223-41. doi: 10.1007/978-3-0346-0228-0_16.
Many tumours of neuroendocrine origin, and also an increasing number of non-neuroendocrine cancers, have been shown to express neuropeptides and/or their corresponding receptors. These peptides and receptors represent the molecular basis for in vivo diagnostic or therapeutic targeting of cancer with radiolabelled or cytotoxic peptide analogues. Galanin is a classical neuropeptide that functions in diverse physiological processes such as food intake, nociception, and blood pressure regulation, and it can also act as a growth factor for neurons. Expression of galanin peptide has been detected in pheochromocytoma, pituitary adenoma, neuroblastic tumours, gastrointestinal cancer, squamous cell carcinoma, brain tumours, melanoma, breast cancer and embryonal carcinoma. In several cancers and tumour cell lines expression of galanin receptors--three are known (GalR1, 2 and 3)--has been shown as well. Expression of peptide or receptors has been correlated with tumour stage or subtypes of pituitary adenoma, neuroblastic tumours, colon carcinoma and squamous cell carcinoma. Galanin treatment has tumour-reducing effects in murine models of gastrointestinal cancer, whereas in animal experiments on adenoma formation, galanin seems to act as a growth factor, promoting both proliferation and tumour formation. In cell culture experiments on tumour cell lines, galanin has shown growth promoting or inhibiting effects. Activation of GalR1 is generally anti-proliferative, whereas activation of GalR2 can have pro- or anti-proliferative effects. Therefore, galanin and its receptors are promising targets for diagnosis and treatment of several types of tumours.
许多神经内分泌起源的肿瘤,以及越来越多的非神经内分泌癌症,已被证明可表达神经肽和/或其相应受体。这些肽和受体是利用放射性标记或细胞毒性肽类似物对癌症进行体内诊断或治疗靶向的分子基础。甘丙肽是一种经典的神经肽,在多种生理过程中发挥作用,如食物摄入、痛觉感受和血压调节,它还可作为神经元的生长因子。在嗜铬细胞瘤、垂体腺瘤、神经母细胞瘤、胃肠道癌、鳞状细胞癌、脑肿瘤、黑色素瘤、乳腺癌和胚胎癌中已检测到甘丙肽的表达。在几种癌症和肿瘤细胞系中也已显示出甘丙肽受体(已知有三种,即GalR1、GalR2和GalR3)的表达。肽或受体的表达与垂体腺瘤、神经母细胞瘤、结肠癌和鳞状细胞癌的肿瘤分期或亚型相关。甘丙肽治疗在胃肠道癌的小鼠模型中具有肿瘤缩小作用,而在腺瘤形成的动物实验中,甘丙肽似乎作为一种生长因子,促进增殖和肿瘤形成。在肿瘤细胞系的细胞培养实验中,甘丙肽已显示出促生长或抑制生长的作用。GalR1的激活通常具有抗增殖作用,而GalR2的激活可具有促增殖或抗增殖作用。因此,甘丙肽及其受体是几种类型肿瘤诊断和治疗的有前景的靶点。