Melanoma exosomes promote mixed M1 and M2 macrophage polarization.
Melanoma exosomes promote mixed M1 and M2 macrophage polarization.
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DOI：
10.1016/j.cyto.2018.02.002
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发表时间：
2018-05
期刊：
影响因子：
3.8
通讯作者：
Hood JL
中科院分区：
文献类型：
--
作者：
Bardi GT;Smith MA;Hood JL
巨噬细胞是黑色素瘤生长和生存的关键参与者。一般来说，巨噬细胞可分为M1或M2活化表型。越来越多的证据表明，黑色素瘤外泌体也促进肿瘤存活和转移。然而，黑色素瘤外泌体在直接影响巨噬细胞功能中的作用知之甚少。在此，我们研究了天然黑色素瘤外泌体可能直接影响巨噬细胞极化的假设。为了探索这一假设，使用黑色素瘤外泌体（B16-F10）的确定来源在体外进行ELISA、RT-qPCR和巨噬细胞功能研究。在RAW264.7巨噬细胞中黑素瘤外泌体诱导常见的M1和M2细胞因子的ELISA结果显示，黑素瘤外泌体并不专门在M1或M2方向上对巨噬细胞进行诱导。黑色素瘤exosomes分别诱导M1和M2代表性细胞因子TNF-α和IL-10。使用具有RAW 264.7和原代巨噬细胞的RT-qPCR阵列的进一步评估证实并扩展了ELISA结果。M1和M2极化表型共同的标志物上调包括CCL 22、IL-12 B、IL-1β、IL-6、i-NOS和TNF-α。M2细胞因子TGF-β在原代巨噬细胞中上调，但在RAW 264.7巨噬细胞中未上调。促肿瘤功能已归因于这些标志物中的每一个。巨噬细胞功能测定表明i-NOS（M1）转化为NOS（M2）活性呈增加趋势。总的来说，这些结果提供了第一个证据，即黑色素瘤外泌体可以诱导混合的M1和M2促肿瘤巨噬细胞活化表型。
Macrophages are key participants in melanoma growth and survival. In general, macrophages can be classified as M1 or M2 activation phenotypes. Increasing evidence demonstrates that melanoma exosomes also facilitate tumor survival and metastasis. However, the role of melanoma exosomes in directly influencing macrophage function is poorly understood. Herein, we investigated the hypothesis that natural melanoma exosomes might directly influence macrophage polarization. To explore this hypothesis, ELISA, RT-qPCR, and macrophage functional studies were performed in vitro using an established source of melanoma exosomes (B16-F10). ELISA results for melanoma exosome induction of common M1 and M2 cytokines in RAW264.7 macrophages, revealed that melanoma exosomes do not polarize macrophages exclusively in the M1 or M2 direction. Melanoma exosomes induced the M1 and M2 representative cytokines TNF-α and IL-10 respectively. Further assessment, using an RT-qPCR array with RAW264.7 and primary macrophages, confirmed and extended the ELISA findings. Upregulation of markers common to both M1 and M2 polarization phenotypes included CCL22, IL-12B, IL-1β, IL-6, i-NOS, and TNF-α. The M2 cytokine TGF-β was upregulated in primary but not RAW264.7 macrophages. Pro-tumor functions have been attributed to each of these markers. Macrophage functional assays demonstrated a trend toward increased i-NOS (M1) to arginase (M2) activity. Collectively, the results provide the first evidence that melanoma exosomes can induce a mixed M1 and M2 pro-tumor macrophage activation phenotype.
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影响因子：
3.3
作者：
Gao J;Wang D;Liu D;Liu M;Ge Y;Jiang M;Liu Y;Zheng D
通讯作者：
Zheng D
影响因子：
11.2
作者：
Gopinathan G;Milagre C;Pearce OM;Reynolds LE;Hodivala-Dilke K;Leinster DA;Zhong H;Hollingsworth RE;Thompson R;Whiteford JR;Balkwill F
通讯作者：
Balkwill F
影响因子：
4.7
作者：
Hood JL
通讯作者：
Hood JL
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影响因子：
5
作者：
Gao, Shanshan;Zhou, Juan;Yuan, Zuyi
通讯作者：
Yuan, Zuyi
DOI：
10.1161/atvbaha.116.307830
发表时间：
2016-09-01
影响因子：
8.7
作者：
Aarup, Annemarie;Pedersen, Tanja X.;Nielsen, Lars B.
通讯作者：
Nielsen, Lars B.