Extracellular vesicles derived from mesenchymal stem cells suppress breast cancer progression by inhibiting angiogenesis.

Abstract

Previous studies have highlighted the antitumor effects of mesenchymal stem cell‑derived extracellular vesicles (MSC‑EVs), positioning them as a promising therapeutic avenue for cancer treatment. However, some researchers have proposed a bidirectional influence of MSC‑EVs on tumors, determined by the specific tissue origin of the MSCs and the types of tumors involved. The present study aimed to elucidate the effects of human placenta MSC‑derived extracellular vesicles (hPMSC‑EVs) on the malignant behavior of a mouse breast cancer model of 4T1 cells in vitro and in vivo. The findings revealed that hPMSC‑EVs significantly inhibited the proliferation, migration and colony formation of cultured 4T1 mouse breast cancer cells without inducing apoptosis. Exposure to conditioned medium from 4T1 cells pretreated with hPMSC‑EVs resulted in decreased angiogenic activity, accompanied by the downregulation of angiogenesis‑promoting genes in human umbilical vein endothelial cells. In murine xenograft models derived from the 4T1 cell line, local administration of hPMSC‑EVs substantially hindered tumor growth. Further results revealed that hPMSC‑EVs inhibited angiogenesis in vivo, as reflected by the use of a vascular growth factor receptor 2‑Fluc transgenic mouse model. In summary, the results confirmed that hPMSC‑EVs negatively modulated breast cancer growth by suppressing tumor cell proliferation and migration via an indirect antiangiogenic mechanism. These results underscored the therapeutic potential of EVs, suggesting a promising avenue for alternative anticancer treatments in the future.