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扁桃体来源的间充质基质细胞来源的细胞外囊泡通过 miR-199a-3p 发挥抗肿瘤作用。

Extracellular vesicles from tonsil‑derived mesenchymal stromal cells show anti‑tumor effect via miR‑199a‑3p.

机构信息

Department of Microbiology, College of Medicine, Ewha Womans University, Seoul 07804, Republic of Korea.

Department of Orthopaedic Surgery, College of Medicine, Ewha Womans University, Seoul 07804, Republic of Korea.

出版信息

Int J Mol Med. 2021 Dec;48(6). doi: 10.3892/ijmm.2021.5054. Epub 2021 Oct 22.


DOI:10.3892/ijmm.2021.5054
PMID:34676871
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8559701/
Abstract

Mesenchymal stem cells (MSCs) are mesoderm‑originated adult SCs that possess multidirectional differentiation potential. MSCs migrate to injured tissue and secrete a range of paracrine factors that induce regeneration in damaged tissue and exert immune modulation. Because tumor progression is dependent on cross‑talk between the tumor and its microenvironment, MSCs also produce extracellular vesicles (EVs) that mediate information transfer in the tumor microenvironment. However, the effect of MSC‑derived EVs on tumor development and progression is still controversial. To date, tonsil‑derived MSCs (T‑MSCs) have been shown to possess all the defined characteristics of MSCs and show distinctive features of differential potential and immune modulation. To observe the effect of soluble mediators from T‑MSCs on tumor growth, human liver cancer cell line (HepG2) cells were injected into nude mice and HepG2 cell scratch migration assay was performed using conditioned medium (CM) of T‑MSCs. T‑MSC CM inhibited tumor growth and progression and it was hypothesized that EVs from T‑MSCs could inhibit tumor progression. microRNA (miRNA or miR) sequencing using five different origins of T‑MSC‑derived EVs was performed and highly expressed miRNAs, such as miR‑199a‑3p, miR‑214‑3p, miR‑199a‑5p and miR‑199b‑5p, were selected. T‑MSCs inhibited tumor growth and HepG2 cell migration, potentially via miR‑199a‑3p targeting CD151, integrin α3 and 6 in HepG2 cells.

摘要

间充质干细胞(MSCs)是中胚层起源的成体干细胞,具有多向分化潜能。MSCs 迁移到受损组织,并分泌一系列旁分泌因子,诱导受损组织再生,并发挥免疫调节作用。由于肿瘤的进展依赖于肿瘤与其微环境之间的串扰,MSCs 还产生细胞外囊泡(EVs),介导肿瘤微环境中的信息传递。然而,MSC 衍生的 EVs 对肿瘤发展和进展的影响仍存在争议。迄今为止,扁桃体来源的间充质干细胞(T-MSCs)已被证明具有 MSC 的所有定义特征,并表现出分化潜能和免疫调节的独特特征。为了观察 T-MSCs 来源的可溶性介质对肿瘤生长的影响,将人肝癌细胞系(HepG2)细胞注射到裸鼠体内,并使用 T-MSCs 的条件培养基(CM)进行 HepG2 细胞划痕迁移实验。T-MSC CM 抑制肿瘤生长和进展,推测 T-MSCs 的 EVs 可以抑制肿瘤进展。使用来自五个不同来源的 T-MSC 衍生 EV 的 microRNA(miRNA 或 miR)测序,选择高度表达的 miRNA,如 miR-199a-3p、miR-214-3p、miR-199a-5p 和 miR-199b-5p。T-MSCs 抑制肿瘤生长和 HepG2 细胞迁移,可能通过 miR-199a-3p 靶向 HepG2 细胞中的 CD151、整合素 α3 和 6。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c84/8559701/c12cfed0e5fc/IJMM-48-06-05054-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c84/8559701/7b876f8a6a10/IJMM-48-06-05054-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c84/8559701/38f46969a9e3/IJMM-48-06-05054-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c84/8559701/713b3e6b244a/IJMM-48-06-05054-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c84/8559701/c12cfed0e5fc/IJMM-48-06-05054-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c84/8559701/7b876f8a6a10/IJMM-48-06-05054-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c84/8559701/38f46969a9e3/IJMM-48-06-05054-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c84/8559701/713b3e6b244a/IJMM-48-06-05054-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c84/8559701/c12cfed0e5fc/IJMM-48-06-05054-g03.jpg

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[5]
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[6]
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[7]
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[8]
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本文引用的文献

[1]
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Adv Drug Deliv Rev. 2021-9

[2]
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Dual Role of MSC-Derived Exosomes in Tumor Development.

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Cell Commun Signal. 2020-9-11

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Conditioned Medium from Human Tonsil-Derived Mesenchymal Stem Cells Enhances Bone Marrow Engraftment via Endothelial Cell Restoration by Pleiotrophin.

Cells. 2020-1-15

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Front Immunol. 2018-12-4

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Mesenchymal stem cells in preclinical cancer cytotherapy: a systematic review.

Stem Cell Res Ther. 2018-12-7

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