Mesenchymal stem cells seldomly fuse with hepatocellular carcinoma cells and are mainly distributed in the tumor stroma in mouse models
Mesenchymal stem cells seldomly fuse with hepatocellular carcinoma cells and are mainly distributed in the tumor stroma in mouse models
复制标题
在小鼠模型中，间充质干细胞很少与肝细胞癌细胞融合，主要分布在肿瘤基质中。
DOI：
10.3892/or.2012.2174
复制
发表时间：
2013-02-01
期刊：
影响因子：
4.2
通讯作者：
Qin, Lun-Xiu
中科院分区：
文献类型：
--
作者：
Li, Guo-Cai;Ye, Qing-Hai;Qin, Lun-Xiu
间充质干细胞（MSCs）可以影响人类恶性肿瘤的生长和转移，包括肝细胞癌（HCC）；然而，它们的作用机制尚不完全清楚。来自骨髓的干细胞与其他细胞的细胞融合越来越受到重视。本研究的目的是研究MSCs在小鼠肝癌模型中的分布，以及MSCs与HCC细胞的融合情况。我们用绿色荧光蛋白（GFP）、红色荧光蛋白（RFP）、4′，6-二氨基-2-苯基吲哚（DAPI）和5-溴-2′-脱氧尿苷（BrdU）标记HCC细胞和间充质干细胞。我们发现MSCs在体外与HCC细胞融合的频率较低。静脉注射MSCs后发现MSCs与HCC组织融合，与未注射MSCs的小鼠相比，MSCs主要分布在肿瘤间质中；注射MSCs后，发现肿瘤间质增大，注射MSCs组肺转移率（20%）明显低于未注射MSCs组（100%，P=0.01）。这些数据表明，MSCs在移植后与HCC的细胞融合并不是MSCs的主要作用机制之一，而间质分化是MSCs的主要作用机制，从而抑制HCC的肺转移。
Mesenchymal stem cells (MSCs) can have an effect on the growth and metastasis of human malignancies, including hepatocellular carcinoma (HCC); however, their mechanisms of action are not yet fully understood. The cell fusion of stem cell derived from bone marrow with other cells has been increasingly emphasized. The purpose of this study was to investigate the distribution of MSCs in mouse models of HCC, as well as the cell fusion between MSCs and HCC cells. We labeled HCC cells and MSCs with green fluorescence protein (GFP), red fluorescence protein (RFP), 4',6-diamidino-2-phenylindole (DAPI) and 5-bromo-2'-deoxyuridine (BrdU). We found that MSCs fused with HCC cells at a low frequency in vitro. MSCs were found to be merged into HCC tissues after intravenous injection, and compared with the mice not injected with MSCs, the MSCs were mainly distributed in the tumor stroma; Following the injection of the MSCs, the tumor stroma was found to have expanded in size, and the rate of pulmonary metastasis in the MSC-injected group was significantly lower (20%) compared to that in the group not injected with MSCs (100%, P=0.01). These data suggest that cell fusion between MSCs and HCC after engraftment is not one of the main mechanisms of action of the MSCs, while stromal differentiation is a major mechanism of action of the MSCs, leading to the inhibition of the pulmonary metastasis of HCC.