在黑色素瘤中，癌相关成纤维细胞（CAF）是肿瘤微环境中的重要细胞成分，因为它们具有促进肿瘤生长和恶性细胞转移扩散的潜力。黑色素瘤细胞能够通过释放细胞外囊泡（EV）来影响微环境中的非肿瘤细胞。将正常真皮成纤维细胞 (NHDF) 重编程为 CAF 的机制仍不完全清楚。然而，它可能被认为是由黑色素瘤特异性 miRNA 介导的，这些 miRNA 由黑色素瘤细胞衍生的 EV 转运。因此，我们想知道黑色素瘤细胞分泌的 EV 中最丰富的 miRNA 之一 miR-92b-3p 是否参与正常成纤维细胞向 CAF 的转化。我们观察到，黑色素瘤细胞来源的 EV 确实将 miR-92b-3p 传递到 NHDF 中，并且其积累与 CAF 形成相关，如 CAF 标记基因表达增强以及增殖和迁移增加所证明的那样。 NHDF 中 miR-92b-3p 的过表达显示出类似的结果，而缺乏 miR-92b-3p 的 EV 不会诱导 CAF 表型。我们确定了 PTEN 作为靶点，其抑制导致 CAF 标记物表达增加。因此，我们提供了一种新的细胞间通讯途径，黑色素瘤细胞通过 EV 转运的 miRNA 控制 CAF 的转化。© 2024 作者。 《Journal of Extracellular Vesicles》由 Wiley periodicals, LLC 代表国际细胞外囊泡学会出版。

In melanoma, carcinoma-associated fibroblasts (CAFs) are important cellular components in the tumour microenvironment due to their potential to promote tumour growth and metastatic spread of malignant cells. Melanoma cells have the ability to affect non-tumour cells in the microenvironment by releasing extracellular vesicles (EVs). The mechanisms responsible for reprogramming normal dermal fibroblasts (NHDFs) into CAFs remain incompletely understood. However, it is likely thought to be mediated by melanoma-specific miRNAs, which are transported by EVs derived from melanoma cells. Therefore, we wondered if one of the most enriched miRNAs in EVs secreted by melanoma cells, miR-92b-3p, is involved in the conversion of normal fibroblasts into CAFs. We observed that melanoma cell-derived EVs indeed delivered miR-92b-3p into NHDFs and that its accumulation correlated with CAF formation, as demonstrated by enhanced expression of CAF marker genes and increased proliferation and migration. Overexpression of miR-92b-3p in NHDFs revealed similar results, while EVs deficient of miR-92b-3p did not induce a CAF phenotype. As a target we identified PTEN, whose repression led to increased expression of CAF markers. We thus provide a novel pathway of intercellular communication by which melanoma cells control the transformation of CAFs by virtue of EV-transported miRNAs.© 2024 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles.