Abstract
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.