Tumor malignancy by genetic transfer between cells forming cell-in-cell structures.
Tumor malignancy by genetic transfer between cells forming cell-in-cell structures.
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DOI：
10.1038/s41419-023-05707-1
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发表时间：
2023-03-13
影响因子：
9
通讯作者：
He M
中科院分区：
文献类型：
--
作者：
Wang R;Zhong H;Wang C;Huang X;Huang A;Du N;Wang D;Sun Q;He M
细胞中细胞结构（Cell-in-cell structures，CIC）是指一种独特的结构，其中一个或多个细胞位于另一个细胞内，其生物学结果知之甚少。本研究旨在探讨CIC形成对肿瘤进展的影响。使用遗传标记的肝细胞癌细胞系，我们探讨了肿瘤细胞可能从经历CIC形成的亲本细胞获得遗传信息和恶性表型的可能性。本研究表明，衍生物，分离自CIC之间形成的两个亚群之间的流式细胞仪分选，被发现继承了从亲本细胞的攻击性特征，表现出增加的能力，在增殖和侵袭。与亲本细胞相比，CIC克隆表达较低水平的E-cadherin，而表达较高水平的Vimentin、ZEB-1、Fibronectin、MMP 9、MMP 2和Snail，表明存在上皮-间充质转化。值得注意的是，新衍生物在异种移植小鼠模型中表现出显著增强的致瘤性。此外，全外显子组测序分析确定了一组潜在的基因，参与CIC介导的遗传转移。这些结果与通过CIC形成的遗传转移在肿瘤细胞的基因组不稳定性和恶性程度中的作用一致，这表明CIC的形成可能在肿瘤进展期间促进遗传转移和恶性程度的获得。
Cell-in-cell structures (CICs) refer to a type of unique structure with one or more cells within another one, whose biological outcomes are poorly understood. The present study aims to investigate the effects of CICs formation on tumor progression. Using genetically marked hepatocellular cancer cell lines, we explored the possibility that tumor cells might acquire genetic information and malignant phenotypes from parental cells undergoing CICs formation. The present study showed that the derivatives, isolated from CICs formed between two subpopulations by flow cytometry sorting, were found to inherit aggressive features from the parental cells, manifested with increased abilities in both proliferation and invasiveness. Consistently, the CICs clones expressed a lower level of E-cadherin and a higher level of Vimentin, ZEB-1, Fibronectin, MMP9, MMP2 and Snail as compared with the parental cells, indicating epithelial-mesenchymal transition. Remarkably, the new derivatives exhibited significantly enhanced tumorigenicity in the xenograft mouse models. Moreover, whole exome sequencing analysis identified a group of potential genes which were involved in CIC-mediated genetic transfer. These results are consistent with a role of genetic transfer by CICs formation in genomic instability and malignancy of tumor cells, which suggest that the formation of CICs may promote genetic transfer and gain of malignancy during tumor progression.
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