胎盘细胞外囊泡在体外移植模型中诱导卵巢肿瘤细胞死亡：可能的治疗潜力。

IF 3 2区医学 Q2 DEVELOPMENTAL BIOLOGY

Placenta Pub Date : 2025-02-01 DOI:10.1016/j.placenta.2024.12.028

Xinyi Sun , Jiayi Wan , Yi Zhang , Ye Shen , Yunhui Tang , Yongxiang Yin , Lawrence W. Chamley , Min Zhao , Qi Chen

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引用次数: 0

摘要

胎盘细胞外囊泡（EVs）是胎盘释放的脂质封闭颗粒，可以促进细胞间的通讯，根据大小分为微型或纳米级EVs。胎盘EVs含有与细胞增殖和死亡相关的分子。在这项研究中，我们研究了用胎盘ev处理人卵巢肿瘤外植体是否能诱导卵巢肿瘤细胞死亡。方法：收集人卵巢肿瘤标本。胎盘ev直接作用于人卵巢肿瘤外植体后，HE染色观察到卵巢肿瘤外植体细胞坏死。测量细胞死亡相关的mirna。结果：外植体暴露于胎盘ev后，细胞凋亡和衰老相关蛋白NF-κβ和γ H2AX的表达显著增加，而增殖相关蛋白的表达显著降低。此外，报道中促进卵巢癌细胞凋亡或抑制卵巢癌细胞生长的miRNA-519a-5p、miRNA-512-3p和miRNA-143-3p在胎盘ev暴露后的外植体中显著升高，miRNA-519a-5p和miRNA-512-3p的靶基因显著降低。用miRNA-519a-5p或miRNA-143-3p模拟物转染SK-OV-3卵巢癌细胞可降低这些细胞的活力。讨论：我们的研究表明胎盘EVs可诱导卵巢肿瘤外植体坏死。暴露于胎盘ev后，细胞凋亡、衰老相关蛋白和mirna水平的增加可能导致卵巢肿瘤细胞表型的变化。

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Placental extracellular vesicles induce ovarian tumour cell death in an ex vivo explant model: Possible therapeutic potential

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Placental extracellular vesicles induce ovarian tumour cell death in an ex vivo explant model: Possible therapeutic potential

Introduction

Placental extracellular vesicles (EVs), lipid-enclosed particles released from the placenta, can facilitate intercellular communication and are classified as micro- or nano-EVs depending on size. Placental EVs contain molecules associated with cell proliferation and death. In this study, we investigated whether treating human ovarian tumour explants with placental EVs could induce ovarian tumour cell death.

Methods

Human ovarian tumours were collected. After directly treating human ovarian tumour explants with placental EVs, cellular necrosis was observed in ovarian tumour explants by HE stains. Cell death-associated miRNAs were measured.

Results

Expression of apoptosis and senescence-associated proteins, including NF-

κ β

and

γ

H2AX, were significantly increased, while proliferation-associated proteins were significantly reduced in the explants after exposure to placental EVs. Furthermore, miRNA-519a-5p, miRNA-512–3p and miRNA-143–3p, which were reported to promote ovarian cancer cell apoptosis or inhibition of ovarian cancer cell growth, were significantly increased, and the target genes of miRNA-519a-5p and miRNA-512–3p were significantly reduced in the explants after exposure to placental EVs. Transfection of SK-OV-3 ovarian cancer cells with a mimic of miRNA-519a-5p or miRNA-143–3p reduced the viability of these cells.

Discussion

Our study demonstrated that placental EVs could induce necrosis in ovarian tumour explants. Increased levels of apoptosis and senescence-associated proteins and miRNAs could contribute to this change in ovarian tumour cell phenotype after exposure to placental EVs.

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来源期刊

Placenta 医学-发育生物学

CiteScore

6.30

自引率

10.50%

发文量

391

审稿时长

78 days

期刊介绍： Placenta publishes high-quality original articles and invited topical reviews on all aspects of human and animal placentation, and the interactions between the mother, the placenta and fetal development. Topics covered include evolution, development, genetics and epigenetics, stem cells, metabolism, transport, immunology, pathology, pharmacology, cell and molecular biology, and developmental programming. The Editors welcome studies on implantation and the endometrium, comparative placentation, the uterine and umbilical circulations, the relationship between fetal and placental development, clinical aspects of altered placental development or function, the placental membranes, the influence of paternal factors on placental development or function, and the assessment of biomarkers of placental disorders.