癌相关成纤维细胞（CAFs）在肿瘤微环境中发挥极为关键的作用，但癌细胞诱导成纤维细胞发生表型转化的分子机制尚未阐明。我们前期的研究证实，黑色素瘤微囊泡能诱导成纤维细胞表型转化并参与微环境改造。本课题进一步提出“黑色素瘤外泌体介导的miRNA內吞能够调控成纤维细胞的重编程及其促血管表型转化”，并重点探讨：①黑色素瘤外泌体诱导成纤维细胞促血管表型转化研究；②黑色素瘤外泌体miRNA在成纤维细胞促血管表型转化中的作用研究；③黑色素瘤外泌体miRNA对成纤维细胞Ets2表达的调控研究；④黑色素瘤外泌体miRNA调控成纤维细胞Ets2表达过程中的信号转导机制研究。本项目将介导的细胞通讯、miRNA调控及细胞重编程三者联系起来，有望揭示黑色素瘤外泌体诱导成纤维细胞促血管生成表型的全新分子机制，对深入阐明肿瘤-间质对话、肿瘤血管生成及miRNA调控机制也具有重要科学意义。

It is reported that carcinoma-associated fibroblasts (CAFs) play critical roles in tumor microenvironment. However, little is known about the molecular mechanisms underlying the transformation of normal fibroblasts to CAFs. Our previous study confirmed that melanoma-derived microvesicles are able to educate the normal fibroblasts to tumor supported fibroblast which is involved in microenvironment remodeling. In conjunction with other findings, we propose that tumoral exosome-containing miRNA mediates the reprogrammed proangiogenic phenotype in CAFs. This project aimed mainly to investigate: ⅰ) roles of melanoma-released exosomes in triggering normal fibroblasts toward proangiogenic CAFs；ⅱ) roles of melanoma exosome-containing miRNA in the acquisition of proangigenic properties in CAFs；ⅲ) regulation of melanoma exosomal miRNA on the transcription factor Ets2 in fibroblasts；and ⅳ) signal pathway involved in melanoma exosomal miRNA-mediated Ets2 uprengulatiuon in fibroblasts. The current project orchestrates the concept of tumoral exosomes-mediated intercellular communication, cell reprogramming and miRNA. The results are expected to reveal a novel mechanism responsible for the formation of proangiogenic phenotype in CAFs, and may contribute to better understanding of tumor-stromal crosstalk, tumor angiogenesis as well as miRNA-governed gene regulation.