Human mesenchymal stem cells inhibit metastasis of a hepatocellular carcinoma model using the MHCC97-H cell line
Human mesenchymal stem cells inhibit metastasis of a hepatocellular carcinoma model using the MHCC97-H cell line
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DOI：
10.1111/j.1349-7006.2010.01738.x
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发表时间：
2010-12-01
期刊：
影响因子：
5.7
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(MSC)对包括肝细胞癌(HCC)在内的人类恶性肿瘤的生长和转移的影响存在争议，其潜在机制尚不清楚。本研究的目的是探讨间充质干细胞在肝细胞癌进展中的作用。我们研究了MSC对高转移潜能的MHCC97-H肝癌细胞体外增殖、侵袭、体内肿瘤生长和肺转移的影响。同时检测转化生长因子-β1(TGF-β1)和基质金属蛋白酶的表达水平及其与MSC对肝癌细胞作用的关系。MHCC97-H细胞与MSC条件培养液共培养可显著促进体外增殖，但抑制侵袭能力。在对荷人肝癌裸鼠模型进行MSC治疗后，MSC主要位于肝癌组织中。与对照组相比，骨髓间充质干细胞治疗组小鼠的肿瘤体积显著增大(3080.51±1234.78 mm~3 vs 2223.75±1000.60 mm~3，P=0.045)，但肺转移细胞数显著减少(49.75±18.86vs 227.22±74.67，P=0.046)。在经MSC处理的肝癌细胞中，转化生长因子β1和基质金属蛋白酶-2的表达显著下调。转化生长因子βsiRNA同时下调肝癌细胞中转化生长因子β和基质金属蛋白酶-2的表达，并阻断MSC诱导的MHCC97-H细胞的增殖和侵袭。MSC促进肿瘤生长，但明显抑制肝癌的侵袭和转移，可能是通过下调转化生长因子β1的表达。这些结果提示，MSC在控制肝癌的转移复发方面可能是有用的。(《癌症科学》2010；101：2546-2553)。
The effects of mesenchymal stem cells (MSC) on the growth and metastasis of human malignancies including hepatocellular carcinoma (HCC) are controversial, and the underlying mechanisms are not yet understood. The aim of this study was to explore the role of MSC in the progression of HCC. We investigated the effect of MSC on in vitro proliferation and invasion and in vivo tumor growth and pulmonary metastasis of MHCC97-H HCC cells with a high metastatic potential. The mRNA and protein levels of transforming growth factor-beta 1 (TGF beta 1) and MMP, and their association with the effects of MSC on HCC cells were also evaluated. Co-culture of MHCC97-H cells with MSC conditioned medium significantly enhanced in vitro proliferation but inhibited invasiveness. Following MSC treatment of a nude mouse model bearing human HCC, the MSC were predominantly located in the HCC tissues. Compared with controls, MSC-treated mice exhibited significantly larger tumors (3080.51 +/- 1234.78 mm3vs 2223.75 +/- 1000.60 mm3, P = 0.045), but decreased cellular numbers of lung metastases (49.75 +/- 18.86 vs 227.22 +/- 74.67, P = 0.046). Expression of TGF beta 1 and MMP-2 was significantly downregulated in the MSC-treated HCC cells. TGF beta siRNA concurrently downregulated expression of TGF beta and MMP-2 in HCC cells and blocked the MSC-induced proliferation and invasiveness of MHCC97-H cells. The MSC enhanced tumor growth but significantly inhibited the invasiveness and metastasis of HCC, possibly through downregulation of TGF beta 1. These findings suggest that MSC could be useful in controlling metastatic recurrence of HCC. (Cancer Sci 2010; 101: 2546-2553).