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脂肪来源的干细胞和癌细胞融合,产生具有更高肿瘤形成能力的癌症干细胞样细胞。

Adipose-derived stem cells and cancer cells fuse to generate cancer stem cell-like cells with increased tumorigenicity.

机构信息

School of Life Sciences, The Chinese University of Hong Kong, Hong Kong, China.

School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China.

出版信息

J Cell Physiol. 2020 Oct;235(10):6794-6807. doi: 10.1002/jcp.29574. Epub 2020 Jan 29.

Abstract

Adipose-derived stem cells (ADSCs) are a type of mesenchymal stem cells isolated from adipose tissue and have the ability to differentiate into adipogenic, osteogenic, and chondrogenic lineages. Despite their great therapeutic potentials, previous studies showed that ADSCs could enhance the proliferation and metastatic potential of breast cancer cells (BCCs). In this study, we found that ADSCs fused with BCCs spontaneously, while breast cancer stem cell (CSC) markers CD44 CD24 EpCAM were enriched in this fusion population. We further assessed the fusion hybrid by multicolor DNA FISH and mouse xenograft assays. Only single nucleus was observed in the fusion hybrid, confirming that it was a synkaryon. In vivo mouse xenograft assay indicated that the tumorigenic potential of the fusion hybrid was significantly higher than that of the parent tumorigenic triple-negative BCC line MDA-MB-231. We had compared the fusion efficiency between two BCC lines, the CD44-rich MDA-MB-231 and the CD44-poor MCF-7, with ADSCs. Interestingly, we found that the fusion efficiency was much higher between MDA-MB-231 and ADSCs, suggesting that a potential mechanism of cell fusion may lie in the dissimilarity between these two cell lines. The cell fusion efficiency was hampered by knocking down the CD44. Altogether, our findings suggest that CD44-mediated cell fusion could be a potential mechanism for generating CSCs.

摘要

脂肪来源的干细胞(ADSCs)是一种从脂肪组织中分离出来的间充质干细胞,具有向脂肪细胞、成骨细胞和软骨细胞分化的能力。尽管具有巨大的治疗潜力,但之前的研究表明 ADSCs 可以增强乳腺癌细胞(BCCs)的增殖和转移潜能。在这项研究中,我们发现 ADSCs 与 BCCs 自发融合,而乳腺癌干细胞(CSC)标志物 CD44 CD24 EpCAM 在融合群体中得到了富集。我们进一步通过多色 DNA FISH 和小鼠异种移植实验评估了融合杂交体。在融合杂交体中仅观察到单个核,证实其为合核体。体内小鼠异种移植实验表明,融合杂交体的致瘤潜力明显高于亲本致瘤性三阴性 BCC 系 MDA-MB-231。我们比较了两种 BCC 系(CD44 丰富的 MDA-MB-231 和 CD44 缺乏的 MCF-7)与 ADSCs 的融合效率。有趣的是,我们发现 MDA-MB-231 与 ADSCs 的融合效率要高得多,这表明细胞融合的潜在机制可能在于这两种细胞系之间的差异。通过敲低 CD44 可以阻碍细胞融合效率。总之,我们的研究结果表明,CD44 介导的细胞融合可能是产生 CSCs 的一种潜在机制。

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