# Extracellular Vesicles from Bone Marrow Mesenchymal Stem Cells Modulate Proliferation, Migration, and Chemosensitivity in Ovarian Cancer Cells

## TL;DR

Bone marrow stem cell vesicles can both help fight ovarian cancer and make it worse, depending on the treatment context.

## Contribution

This study reveals the dual role of BM-MSC-EVs in modulating ovarian cancer progression and chemosensitivity.

## Key findings

- BM-MSC-EVs increased cancer cell proliferation but reduced colony formation, migration, and invasion in vitro.
- EVs sensitized ALDH+ CSC-like cells to carboplatin but had no effect on paclitaxel response.
- In vivo, EVs accelerated tumor growth and activated prosurvival and angiogenic pathways.

## Abstract

Ovarian cancer is the most lethal gynecologic malignancy, with chemoresistance and recurrence driven by cancer stem cells (CSCs). Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) mediate tumor–stroma communication, but their role in ovarian cancer progression and therapy remains unclear. Here, we investigated bone marrow (BM)-MSC-EVs, their effects on ovarian cancer cells, and the underlying molecular mechanisms. BM-MSCs were isolated, confirmed using flow cytometry and trilineage differentiation, and their EVs characterized using nanoparticle tracking analysis, transmission electron microscopy, and Western blotting. Kuramochi cells were treated with BM-MSC-EVs and assessed for proliferation, colony formation, migration, invasion, apoptosis, and chemosensitivity. Aldehyde dehydrogenase (ALDH+) Kuramochi cells, with or without EV exposure, were transplanted into non-obese diabetic severe combined immunodeficiency mice for xenograft studies, followed by histology, immunohistochemistry, Western blotting, and EV miRNA profiling. BM-MSC-EVs increased cancer cell proliferation but reduced colony formation, migration, and invasion in vitro. They sensitized ALDH+ CSC-like cells to carboplatin, while paclitaxel response remained unchanged. In vivo, EVs accelerated tumor growth and activated prosurvival (p-AKT, BCL-2), angiogenic (VEGFA, CD31), and epithelial–mesenchymal transition-associated (vimentin) pathways. EVs were found to be enriched in hsa-miR-100-5p, hsa-miR-122-5p, and hsa-let-7i-5p based on miRNA array analysis, and these findings were further validated by qRT-PCR. These findings reveal the dual roles of BM-MSC-EVs: enhancing carboplatin sensitivity while promoting tumor progression and angiogenesis.