Anti-inflammatory and anti-invasive effects of alpha-melanocyte-stimulating hormone in human melanoma cells.
Anti-inflammatory and anti-invasive effects of alpha-melanocyte-stimulating hormone in human melanoma cells.
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人黑色素瘤细胞中α-核细胞刺激激素的抗炎和抗侵入性作用。
DOI：
10.1038/sj.bjc.6601349
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发表时间：
2003-11-17
影响因子：
8.8
通讯作者：
Mac Neil, S
中科院分区：
文献类型：
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作者：
Eves, P;Haycock, J;Layton, C;Wagner, M;Kemp, H;Szabo, M;Morandini, R;Ghanem, G;Garcia-Borron, J C;Jimenez-Cervantes, C;Mac Neil, S
α黑素细胞刺激素(α-MSH)在哺乳动物体内具有多种营养功能，包括色素、抗炎、解热和免疫调节作用。据报道，α-，β-和γ-MSH的水平与恶性黑色素瘤的发生发展有关，也可以影响黑色素瘤的侵袭，但其他研究表明，α-MSH具有延缓侵袭的作用。在本研究中，我们研究了α-MSH对三种不同转移潜能的人黑色素瘤细胞系(HBL、A375-SM和C8161)的作用。α-黑素细胞类似激素通过纤维连接蛋白和人类重建的HBL系皮肤复合模型减少侵袭性，并抑制促炎细胞因子刺激的NF-κB转录因子的激活。但A375-SM和C8161细胞对α-MSH无反应。免疫荧光显微镜和Western blotting检测到三株细胞均表达黑素皮质素-1受体(MC-1R)，HBL和A375-SM细胞均表达MC-2R。受体结合发现与α-MSH有相似亲和力的三个细胞系在HBL细胞上具有最高数量的结合位点。只有HBL黑色素瘤细胞对α-MSH有明显的环磷酸腺苷(CAMP)反应，但三株黑色素瘤细胞对α-MSH的急性添加(+(−)-N6-(2-苯基异丙基)-腺苷(PIA))均有反应，细胞内钙升高。无反应系表现为MC-1R多态(C8161，Arg(Wt)151/Cys 151；A375-SM，纯合Cys 151)，而HBL系为野生型。用野生型MC-1R稳定转染C8161细胞产生的细胞侵袭力被α-msh显著抑制。根据这些数据，我们得出结论，α-MSH可以减少黑色素瘤细胞的侵袭，并保护细胞免受具有野生型受体的细胞的促炎细胞因子的攻击。
α-Melanocyte stimulating hormone (α-MSH) is known to have pleiotrophic functions including pigmentary, anti-inflammatory, antipyretic and immunoregulatory roles in the mammalian body. It is also reported to influence melanoma invasion with levels of α-, β- and γ-MSH correlated clinically with malignant melanoma development, but other studies suggest α-MSH acts to retard invasion. In the present study, we investigated the action of α-MSH on three human melanoma cell lines (HBL, A375-SM and C8161) differing in metastatic potential. α-melanocyte-simulating hormone reduced invasion through fibronectin and also through a human reconstructed skin composite model for the HBL line, and inhibited proinflammatory cytokine-stimulated activation of the NF-κB transcription factor. However, A375-SM and C8161 cells did not respond to α-MSH. Immunofluorescent microscopy and Western blotting identified melanocortin-1 receptor (MC-1R) expression for all three lines and MC-2R on HBL and A375-SM lines. Receptor binding identified a similar affinity for α-MSH for all three lines with the highest number of binding sites on HBL cells. Only the HBL melanoma line demonstrated a detectable cyclic adenosine monophosphate (cAMP) response to α-MSH, although all three lines responded to acute α-MSH addition (+(−)-N6-(2-phenylisopropyl)-adenosine (PIA)) with an elevation in intracellular calcium. The nonresponsive lines displayed MC-1R polymorphisms (C8161, Arg (wt) 151/Cys 151; A375-SM, homozygous Cys 151), whereas the HBL line was wild type. Stable transfection of the C8161 line with wild-type MC-1R produced cells whose invasion was significantly inhibited by α-MSH. From this data, we conclude that α-MSH can reduce melanoma cell invasion and protect cells against proinflammatory cytokine attack in cells with the wild-type receptor (HBL).