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Extracellular vesicles derived from Wharton’s Jelly mesenchymal stem cells inhibit the tumor environment via the miR-125b/HIF1α signaling pathway

Authors :
Yun-Hsuan Chang
Cat-Khanh Vuong
Nhat-Hoang Ngo
Toshiharu Yamashita
Xiucai Ye
Yasunori Futamura
Mizuho Fukushige
Mana Obata-Yasuoka
Hiromi Hamada
Motoo Osaka
Yuji Hiramatsu
Tetsuya Sakurai
Osamu Ohneda
Source :
Scientific Reports, Vol 12, Iss 1, Pp 1-16 (2022)
Publication Year :
2022
Publisher :
Nature Portfolio, 2022.

Abstract

Abstract Triple negative breast cancer (TNBC) is associated with worse outcomes and results in high mortality; therefore, great efforts are required to find effective treatment. In the present study, we suggested a novel strategy to treat TNBC using mesenchymal stem cell (MSC)-derived extracellular vesicles (EV) to transform the behaviors and cellular communication of TNBC cells (BCC) with other non-cancer cells related to tumorigenesis and metastasis. Our data showed that, BCC after being internalized with EV derived from Wharton’s Jelly MSC (WJ-EV) showed the impaired proliferation, stemness properties, tumorigenesis and metastasis under hypoxic conditions. Moreover, these inhibitory effects may be involved in the transfer of miRNA-125b from WJ-EV to BCC, which downregulated the expression of HIF1α and target genes related to proliferation, epithelial-mesenchymal transition, and angiogenesis. Of note, WJ-EV-internalized BCC (wBCC) showed transformed behaviors that attenuated the in vivo development and metastatic ability of TNBC, the angiogenic abilities of endothelial cells and endothelial progenitor cells and the generation of cancer-associated fibroblasts from MSC. Furthermore, wBCC generated a new EV with modified functions that contributed to the inhibitory effects on tumorigenesis and metastasis of TNBC. Taken together, our findings suggested that WJ-EV treatment is a promising therapy that results in the generation of wBCC to interrupt the cellular crosstalk in the tumor environment and inhibit the tumor progression in TNBC.

Subjects

Subjects :
Medicine
Science

Details

Language :
English
ISSN :
20452322
Volume :
12
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Scientific Reports
Publication Type :
Academic Journal
Accession number :
edsdoj.b31886cf36f46bbba0e0c1d2e6ae2c4
Document Type :
article
Full Text :
https://doi.org/10.1038/s41598-022-17767-y