Background: Intracellular miRNA transfer is an intriguing and lesser-described mode of intracellular communication. Epithelial ovarian carcinoma, of which the high-grade serous histotype represents the most common and deadliest form, is characterized by a microenvironment consisting of tumor and stromal cells, ascitic fluid, and extracellular matrix, presenting a rich milieu of factors that can affect neighboring cells. Methods: We examined the mode of miR transfer in serous ovarian carcinoma cell lines cultured on different extracellular matrix supports both in two-dimensional and three-dimensional formats coupled with traditional, live-cell time-lapse, multiphoton fluorescence imaging modalities, and fluorescence-activated cell sorting approaches. Results: Our data demonstrate that miR can transfer between cells both in culture and in vivo. Moreover, transferred miRNA results in target-specific gene expression changes in recipient cells. Our data indicate that miR transfer occurs via extracellular vesicles, which shuttle from and within the donor and recipient cells via endocytic pathways recruiting sorting, early, late, and recycling endosomes. Conclusions: Our study highlights the phenomenon of miR transfer as a mode of communication between serous ovarian cancer cells, which can affect both treatment and diagnostics of this disease.
背景：细胞内miRNA转移是一种引人注目但较少被描述的细胞间通讯方式。高级别浆液性上皮性卵巢癌作为最常见且致死率最高的亚型，其微环境由肿瘤细胞、基质细胞、腹水及细胞外基质构成，形成了富含影响邻近细胞因子的复杂生态。方法：本研究通过二维与三维细胞外基质培养体系，结合传统活细胞延时成像、多光子荧光显微技术及荧光激活细胞分选法，系统探究了浆液性卵巢癌细胞系中miR的转移模式。结果：数据显示miR在体外培养体系及体内环境中均能实现细胞间转移，且转移后的miRNA能在受体细胞中引发靶向特异性基因表达改变。研究进一步揭示该转移过程通过细胞外囊泡介导，这些囊泡通过内存途径在供体与受体细胞间穿梭，并募集分选内体、早期内体、晚期内体及循环内体共同参与转运过程。结论：本研究揭示了miR转移作为浆液性卵巢癌细胞间通讯的重要机制，该发现可能对该疾病的治疗与诊断策略产生深远影响。
Functional miRNA Transfer in Models of Serous Ovarian Carcinoma
肿瘤(癌症)患者之家