Membrane microvesicles as mediators for melanoma-fibroblasts communication: Roles of the VCAM-1/VLA-4 axis and the ERK1/2 signal pathway
Membrane microvesicles as mediators for melanoma-fibroblasts communication: Roles of the VCAM-1/VLA-4 axis and the ERK1/2 signal pathway
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膜微泡作为黑色素瘤-成纤维细胞通讯的介质：VCAM-1/VLA-4 轴和 ERK1/2 信号通路的作用。
DOI：
10.1016/j.canlet.2015.01.032
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发表时间：
2015-05-01
期刊：
影响因子：
9.7
通讯作者：
Shang, Zheng-jun
中科院分区：
文献类型：
--
作者：
Zhao, Xiao-Ping;Wang, Meng;Shang, Zheng-jun
最近的研究表明，肿瘤微环境中的微泡（MV）正在成为细胞通讯的有效介质。在这项研究中，我们研究了MV介导的正常成纤维细胞转化为肿瘤相关的成纤维细胞，专注于血管细胞粘附分子-1（VCAM-1）表达的功能调节。在与黑素瘤衍生的MV孵育后，成纤维细胞（NIH/3 T3细胞）以ERK 1/2激活依赖的方式呈现VCAM-1表达的明显增强，并且当MV来自高转移性黑素瘤细胞时，这种增强进一步增强。粘附分析表明，VCAM-1/VLA-4轴参与了高转移性黑色素瘤细胞和BMSC对MV-教育的成纤维细胞的优先附着。低氧通过直接上调高转移性黑素瘤细胞中VLA-4的表达和通过黑素瘤释放的MV间接激发成纤维细胞中VCAM-1的表达来促进黑素瘤-成纤维细胞相互作用。此外，MV-教育的成纤维细胞增加IL-6，成纤维细胞活化蛋白和EGF的表达同时。MVs的蛋白质组学分析表明，除了MAPK信号通路之外，许多信号通路也受到黑色素瘤MVs的调节，MVs作为参与黑色素瘤进展的肿瘤信使发挥作用。(C)2015爱思唯尔爱尔兰有限公司版权所有。
Recent studies suggest that microvesicles (MVs) within the tumor microenvironment are emerging as potent mediators for cell cell communication. In this study, we investigated the MV-mediated transformation of normal fibroblasts to tumor-associated fibroblasts, focusing on the functional regulation of vascular cell adhesion molecule-1 (VCAM-1) expression. After incubation with melanoma-derived MVs, the fibroblasts (NIH/3T3 cells) presented an obvious enhancement of VCAM-1 expression in an ERK1/2-activation-dependent manner, and this enhancement was further increased when the MVs were from highly metastatic melanoma cells. The adhesion analysis showed that the VCAM-1/VLA-4 axis is involved in the preferential attachment of highly metastatic melanoma cells and BMSCs to MV-educated fibroblasts. Hypoxia promoted melanoma-fibroblast interaction by directly upregulating VLA-4 expression in highly metastatic melanoma cells and indirectly provoking VCAM-1 expression in fibroblast cells via melanoma-released MVs. Moreover, MV-educated fibroblasts increased IL-6, fibroblast activation protein and EGF expression simultaneously. Proteomic analysis of MVs suggested that numerous signal pathways in addition to the MAPK signal pathway are regulated by melanoma MVs, which function as tumor messengers that participate in melanoma progression. (C) 2015 Elsevier Ireland Ltd. All rights reserved.