Lincoln D T, Sinowatz F, Kölle S, Takahashi H, Parsons P, Waters M
Department of Medical Sciences, Faculty of Allied Health, Kuwait University, Kuwait.
Anticancer Res. 1999 May-Jun;19(3A):1919-31.
Growth hormone (GH) exerts its regulatory functions in controlling metabolism, balanced growth and differentiated cell expression by acting on specific receptors, which trigger a phosphorylation cascade resulting in the modulation of numerous signalling pathways, and dictate gene expression. Immunohistochemical techniques were used to demonstrate the presence of growth hormone receptors in 126 formalin-fixed, paraffin-embedded melanocytic tumours comprising melanocytic naevi, superficial spreading melanoma, nodular melanoma, lentigo maligna melanoma and metastatic melanomas. The relative proportion of positive cells and intensity of staining was higher in neoplastic cells, compared to normal cutaneous cells. Of the 76 cases of common melanocytic naevi (CMN) studies, 46 were weakly reactive with MAb 263. Heterogeneity of immunoreactivity was found in primary melanoma lesions with a variable range of positive cells. Of 37 cases studied, 34 were moderately to strongly positive. Immunoreactivity showed subcellular localization of the GH-receptor in cell membranes, was predominantly cytoplasmic, but strong nuclear immunoreaction was also apparent in many instances. The nuclear localization of immunoreactivity is the result of nuclear GH-receptor/binding protein, identically to the cytosolic and plasma growth hormone binding protein. Intense immuno-reactivity was also observed in the cellular Golgi area of established cell lines and cultured tissue-derived cells in exponential growth phase, indicating cells are capable of GH-receptor synthesis. In the primary lesions, dermal tumour cells tended to be more immunoreactive relative to those seen in the dermal region. Metastatic lesions in various organs also expressed growth hormone receptors in secondary tumour cells and all of the metastatic cases were positive. The expression of GH-receptors in human melanoma cells means that these cells are directly responsive to GH action and that GH may stimulate local production of IGF-I, which then acts in an autocrine mechanism.
生长激素（GH）通过作用于特定受体发挥其调节功能，控制新陈代谢、平衡生长和分化细胞表达，这些受体引发磷酸化级联反应，导致众多信号通路的调节，并决定基因表达。免疫组织化学技术用于证明生长激素受体在126例福尔马林固定、石蜡包埋的黑素细胞肿瘤中的存在，这些肿瘤包括黑素细胞痣、浅表扩散性黑色素瘤、结节性黑色素瘤、恶性雀斑样痣黑色素瘤和转移性黑色素瘤。与正常皮肤细胞相比，肿瘤细胞中阳性细胞的相对比例和染色强度更高。在76例普通黑素细胞痣（CMN）研究中，46例与单克隆抗体263呈弱反应。在原发性黑色素瘤病变中发现免疫反应性存在异质性，阳性细胞范围可变。在37例研究病例中，34例为中度至强阳性。免疫反应性显示生长激素受体在细胞膜中的亚细胞定位，主要位于细胞质中，但在许多情况下也明显可见强核免疫反应。免疫反应性的核定位是核生长激素受体/结合蛋白的结果，与细胞溶质和血浆生长激素结合蛋白相同。在指数生长期的已建立细胞系和培养的组织来源细胞的细胞高尔基体区域也观察到强烈的免疫反应性，表明细胞能够合成生长激素受体。在原发性病变中，真皮肿瘤细胞相对于真皮区域的细胞往往更具免疫反应性。各种器官中的转移性病变在继发性肿瘤细胞中也表达生长激素受体，所有转移病例均为阳性。人黑色素瘤细胞中生长激素受体的表达意味着这些细胞对生长激素的作用直接有反应，并且生长激素可能刺激胰岛素样生长因子-I的局部产生，然后以自分泌机制发挥作用。
