Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40202, USA.
James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA.
Int J Mol Sci. 2019 Mar 12;20(5):1235. doi: 10.3390/ijms20051235.
Melanoma-derived small extracellular vesicles (sEVs) participate in tumor pathogenesis. Tumor pathogenesis is highly dependent on inflammatory processes. Given the potential for melanoma sEVs to carry tumor biomarkers, we explored the hypothesis that they may contain inflammation-related mRNA content. Biophysical characterization showed that human primary melanocyte-derived sEVs trended toward being smaller and having less negative (more neutral) zeta potential than human melanoma sEVs (A-375, SKMEL-28, and C-32). Using primary melanocyte sEVs as the control population, RT-qPCR array results demonstrated similarities and differences in gene expression between melanoma sEV types. Upregulation of pro-angiogenic chemokine ligand CXCL1, CXCL2, and CXCL8 mRNAs in A-375 and SKMEL-28 melanoma sEVs was the most consistent finding. This paralleled increased production of CXCL1, CXCL2, and CXCL8 proteins by A-375 and SKMEL-28 sEV source cells. Overall, the use of primary melanocyte sEVs as a control sEV reference population facilitated the detection of inflammation-related melanoma sEV mRNA content.
黑素瘤来源的小细胞外囊泡（sEVs）参与肿瘤发病机制。肿瘤发病机制高度依赖于炎症过程。鉴于黑素瘤 sEV 有可能携带肿瘤生物标志物，我们假设它们可能含有与炎症相关的 mRNA 内容。生物物理特性分析表明，与人类黑素瘤 sEV（A-375、SKMEL-28 和 C-32）相比，人原代黑素细胞来源的 sEV 趋向于更小，且负（更中性）zeta 电位更小。使用原代黑素细胞 sEV 作为对照群体，RT-qPCR 阵列结果表明黑素瘤 sEV 类型之间的基因表达存在相似性和差异。A-375 和 SKMEL-28 黑素瘤 sEV 中促血管生成趋化因子配体 CXCL1、CXCL2 和 CXCL8 mRNAs 的上调是最一致的发现。这与 A-375 和 SKMEL-28 sEV 来源细胞中 CXCL1、CXCL2 和 CXCL8 蛋白的产生增加相平行。总体而言，使用原代黑素细胞 sEV 作为对照 sEV 参考群体有助于检测与炎症相关的黑素瘤 sEV mRNA 内容。
