# Functional miRNA Transfer in Models of Serous Ovarian Carcinoma

## TL;DR

This study shows that miRNA can be transferred between ovarian cancer cells through vesicles, influencing gene activity and potentially affecting treatment and diagnosis.

## Contribution

The study reveals that miRNA transfer in serous ovarian carcinoma occurs via extracellular vesicles and is recycled for further cell communication.

## Key findings

- miRNA is transferred between serous ovarian cancer cells via extracellular vesicles.
- Transferred miRNA leads to specific gene expression changes in recipient cells.
- miRNA is likely recycled out of recipient cells via endocytosis for further transfer.

## Abstract

Cancer cells are regulated by multiple genetic and environmental factors. Due to its specific biology, cells of epithelial ovarian carcinoma are immersed in a rich microenvironment consisting of malignant ascites, stromal cells, parenchymal cells, and their secreted factors, indicating the presence of multiple signaling networks regulating cancer cell fates. A lesser-described mode of intracellular communication in ovarian carcinoma is through the transfer of miRNA. Here we describe that miRNA can be transferred between serous ovarian cancer cells via vesicles, and, once inside the cell, it can initiate transcription of the downstream target genes. Our study also indicates that miRNA taken up by the recipient cell is more likely to be recycled out via endocytosis (as opposed to becoming degraded inside the cell), where it can be absorbed by another cell, thus expanding the range of cells that could be potentially affected by this miRNA.

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.