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间充质干细胞来源的细胞外囊泡通过抑制血管生成抑制乳腺癌进展

英文原题:Extracellular vesicles derived from mesenchymal stem cells suppress breast cancer progression by inhibiting angiogenesis.

查看英文原题

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

PubMed 2024/09/02(内容时间) Mol Med Rep Q2 · IF 5(JCR 2025)

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中文摘要

既往研究强调了间充质干细胞来源的细胞外囊泡(MSC EVs)的抗肿瘤作用,将其定位为一种有前景的癌症治疗途径。然而,一些研究者提出MSC EVs对肿瘤具有双向影响,这取决于MSC的特定组织来源和所涉及的肿瘤类型。

本研究旨在阐明人胎盘MSC来源的细胞外囊泡(hPMSC EVs)对4T1细胞小鼠乳腺癌模型体外和体内恶性行为的影响。研究结果显示,hPMSC EVs显著抑制了培养的4T1小鼠乳腺癌细胞的增殖、迁移和集落形成,且未诱导细胞凋亡。暴露于经hPMSC EVs预处理的4T1细胞条件培养基后,人脐静脉内皮细胞的血管生成活性降低,同时血管生成促进基因表达下调。在源自4T1细胞系的小鼠异种移植模型中,局部给予hPMSC EVs显著抑制了肿瘤生长。

进一步结果显示,hPMSC EVs在体内抑制了血管生成,这一点通过使用血管生长因子受体2 Fluc转基因小鼠模型得到证实。

总之,结果证实hPMSC EVs通过间接抗血管生成机制抑制肿瘤细胞增殖和迁移,从而负向调控乳腺癌生长。这些结果凸显了EVs的治疗潜力,为未来替代性抗癌治疗提示了一条有前景的途径。

展开英文摘要原文

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.

论文信息

作者
Zhou M、Li H、Zhao J、Zhang Q、Han Z、Han ZC、Zhu L、Wang H
第一作者单位
Department of Radiation Oncology, Tianjin Union Medical Center, Nankai University, Tianjin 300121, P.R. China; 2School of Medicine, Nankai University, Tianjin 300071, P.R. China.China
通讯作者单位
School of Medicine, Nankai University, Tianjin 300071, P.R. China.China
期刊
Molecular medicine reports2024 Nov
原文标识
PubMed 39219260 · DOI 10.3892/mmr.2024.13316