Zhu Ningwen, Eves Paula C, Katerinaki Effie, Szabo Marika, Morandini Renato, Ghanem Ghanem, Lorigan Paul, MacNeil Sheila, Haycock John W
Department of Engineering Materials, Sir Robert Hadfield Building, Sheffield, UK.
J Invest Dermatol. 2002 Nov;119(5):1165-71. doi: 10.1046/j.1523-1747.2002.19516.x.
We have previously shown alpha-melanocyte stimulating hormone to protect melanocytes and melanoma cells from the proinflammatory actions of tumor necrosis factor-alpha. The aim of the study was to extend this work to look into the influence of tumor necrosis factor-alpha on melanoma cell attachment, invasion, and integrin expression and ask to what extent alpha-melanocyte stimulating hormone might protect cells from tumor necrosis factor-alpha stimulation of increased integrin expression. HBL human melanoma cells were studied under resting and stressed conditions using tumor necrosis factor-alpha as a proinflammatory cytokine. Functional information on the actions of tumor necrosis factor-alpha on melanoma cells was obtained by examining the strength of attachment of melanoma cells to substrates and the ability of melanoma cells to invade through fibronectin. alpha3, alpha4, and beta1 integrin expression was detected by Western immunoblotting and the ability of alpha-melanocyte stimulating hormone to oppose the actions of tumor necrosis factor-alpha was studied on HBL cell attachment, invasion, and integrin subunit expression. Our results show that tumor necrosis factor-alpha increases the number of melanoma cells attaching to collagen (types I and IV) and tissue culture polystyrene, increases ability to invade through fibronectin, and upregulates the expression of alpha3 (28%), alpha4 (90%), and beta1 (65%) integrin subunit expression. In contrast, alpha-melanocyte stimulating hormone reduced cell attachment, invasion, and integrin expression and opposed the stimulatory effects of tumor necrosis factor-alpha. In conclusion this study provides further evidence of alpha-melanocyte stimulating hormone acting to "protect" melanoma cells from proinflammatory cytokine action. Our data support a hypothesis that an inflammatory environment would promote melanoma invasion and that the anti-invasive actions of alpha-melanocyte stimulating hormone are consistent with its working in an anti-inflammatory capacity.
我们之前已经表明，α-黑素细胞刺激素可保护黑素细胞和黑色素瘤细胞免受肿瘤坏死因子-α的促炎作用。本研究的目的是扩展这项工作，以研究肿瘤坏死因子-α对黑色素瘤细胞黏附、侵袭和整合素表达的影响，并探讨α-黑素细胞刺激素在多大程度上可以保护细胞免受肿瘤坏死因子-α刺激导致的整合素表达增加的影响。使用肿瘤坏死因子-α作为促炎细胞因子，在静息和应激条件下研究了HBL人黑色素瘤细胞。通过检测黑色素瘤细胞与底物的黏附强度以及黑色素瘤细胞穿过纤连蛋白的侵袭能力，获得了肿瘤坏死因子-α对黑色素瘤细胞作用的功能信息。通过蛋白质免疫印迹法检测α3、α4和β1整合素的表达，并研究了α-黑素细胞刺激素对抗肿瘤坏死因子-α作用的能力，观察其对HBL细胞黏附、侵袭和整合素亚基表达的影响。我们的结果表明，肿瘤坏死因子-α增加了附着于I型和IV型胶原蛋白以及组织培养聚苯乙烯上的黑色素瘤细胞数量，增强了穿过纤连蛋白的侵袭能力，并上调了α3（28%）、α4（90%）和β1（65%）整合素亚基的表达。相比之下，α-黑素细胞刺激素减少了细胞黏附、侵袭和整合素表达，并对抗肿瘤坏死因子-α的刺激作用。总之，本研究进一步证明了α-黑素细胞刺激素可“保护”黑色素瘤细胞免受促炎细胞因子的作用。我们的数据支持这样一个假设，即炎症环境会促进黑色素瘤的侵袭，而α-黑素细胞刺激素的抗侵袭作用与其抗炎能力的发挥是一致的。
