Human Mesenchymal Stem Cells Inhibit Metastasis Of A Hepatocellular Carcinoma Model Using The Mhcc97-H Cell Line

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).