Cantón Irene, Eves Paula C, Szabo Marika, Vidal-Vanaclocha Fernando, Sisley Karen, Rennie Ian G, Haycock John W, MacNeil Sheila
Section of Human Metabolism, Division of Clinical Sciences (North), Northern General Hospital, Sheffield S5 7AU, UK.
J Invest Dermatol. 2003 Sep;121(3):557-63. doi: 10.1046/j.1523-1747.2003.12417.x.
Iris melanomas are less likely to metastasize than posterior compartment melanomas. The anterior chamber of the eye is an immunosuppressed microenvironment where a wide range of immunosuppressive factors in aqueous humor contribute to the immune privilege. One such factor is alpha-melanocyte-stimulating hormone, a potent anti-inflammatory neuropeptide that exhibits efficacy in many studies of acute and chronic inflammation. The aim of this study was to investigate whether the different metastatic behavior of iris melanomas versus posterior compartment melanomas might be explained by the differing immunosuppressive/anti-inflammatory environments of these tumors in vivo. To investigate this hypothesis, we studied the effect of human aqueous and vitreous fluids, of the proinflammatory cytokine tumor necrosis factor alpha, and of the anti-inflammatory peptides alpha-melanocyte-stimulating hormone and melanocyte-stimulating hormone 11-13 (KP-D-V) on the invasion of three human uveal melanoma cell lines through human fibronectin. Fresh aqueous humor samples significantly decreased the invasion in two out of three uveal melanoma cell lines. In contrast, vitreous humor did not reduce invasion. Tumor necrosis factor alpha significantly increased the invasiveness of uveal melanoma cell lines by approximately 50%-80% over 20 h. Full-length alpha-melanocyte-stimulating hormone, at concentrations present in the aqueous humor (10-9 M), as well as melanocyte-stimulating hormone 11-13 (KP-D-V) reduced the invasion of cells through human fibronectin by 45%-50% and also protected uveal melanoma cells from the pro-invasive actions of tumor necrosis factor alpha. These data are consistent with inflammation playing a major role in affecting the metastatic ability of uveal melanomas. Thus, ocular microenvironments that differ in their immunosuppressive/anti-inflammatory properties may influence the invasiveness of developing tumors.
虹膜黑色素瘤比后房黑色素瘤发生转移的可能性更小。眼球的前房是一个免疫抑制的微环境，房水中多种免疫抑制因子促成了免疫赦免。其中一种因子是α-黑素细胞刺激素，它是一种强效抗炎神经肽，在许多急慢性炎症研究中均显示出疗效。本研究的目的是调查虹膜黑色素瘤与后房黑色素瘤不同的转移行为是否可以用这些肿瘤在体内不同的免疫抑制/抗炎环境来解释。为了验证这一假设，我们研究了人房水和玻璃体、促炎细胞因子肿瘤坏死因子α以及抗炎肽α-黑素细胞刺激素和黑素细胞刺激素11 - 13（KP - D - V）对三种人葡萄膜黑色素瘤细胞系通过人纤连蛋白的侵袭作用的影响。新鲜房水在三种葡萄膜黑色素瘤细胞系中的两种中显著降低了侵袭。相比之下，玻璃体并未降低侵袭。肿瘤坏死因子α在20小时内使葡萄膜黑色素瘤细胞系的侵袭性显著增加了约50% - 80%。房水中存在的浓度（10 - 9 M）的全长α-黑素细胞刺激素以及黑素细胞刺激素11 - 13（KP - D - V）使细胞通过人纤连蛋白的侵袭减少了45% - 50%，并且还保护葡萄膜黑色素瘤细胞免受肿瘤坏死因子α的促侵袭作用。这些数据表明炎症在影响葡萄膜黑色素瘤的转移能力中起主要作用。因此，具有不同免疫抑制/抗炎特性的眼内微环境可能会影响正在形成的肿瘤的侵袭性。
