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.

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.

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