Although MHCC97-L cell line and MHCC97-H cell line have an identical genetic background, in this study, we observed the expression of TGF β1, Smad2 and Smad7 in MHCC97-L cell lines was higher than that in MHCC97-H cell lines both in vitro and in vivo, in addition, MHCC97-L have a slower growth speed in early stage of tumor formation. Our results were in agreement with other documents, which demonstrate TGF β can induce apoptosis of human hepatoma cell line in vitro, and enhance tumor formation by transfection of an antisense TGF-β1 expression vector into cancer cells[24, 25]. Our results suggest that the basic level of TGF β in cell line could affect on its growth, and TGF β1/Smads play an inhibitory role in the course of tumorigenensis.
We also found the TGF β1 protein were positively correlated with pulmonary metastasis in the models, and in mRNA levels, TGF β1 correlated with that of Smad2 and Smad7. Our results were consistent with other studies regarding the association between TGF β1/Smads and HCC metastasis[7, 15, 26], and these results support the veiw that TGF β1/Smads promote pulmonary metastasis of HCC.
The contradict results in this study, inhibitory role in tumorgenesis and promoting role in tumor metastasis, may arise from the dual role of TGF β1 in different stage of cancer development. It has reported during the early stages of tumor formation, TGF β1 acts as a tumor suppressor, inhibiting proliferation and inducing apoptosis of tumor cells. However, during later stages of tumorigenesis, many tumor cells become unresponsive to the growth inhibitory functions of TGF β1, and get more motile, more invasive, and more resistant to apoptosis. In addition, TGF β can stimulate non-invasive HCC cells to acquire invasive phenotypes. Our results support the view that TGF β1/Smads play a dual role in the development of HCC. We also observed MHCC97-L cell lines have a higher TGF β1/Smads levels but a lower metastasis than MHCC97-H cell lines, and both cell lines have an upregulated levels of TGF β1 during the course of metastasis. These results reflected the basic levels of TGF β1 were not the only factor for metastasis, and highlight that the role of TGF β1/Smads should be decided in an active course.
The result that TGF β correlate with pulmonary metastasis in our study will give a new insight to investigate the metastatic mechanism of HCC. The cells in the tumor tissue communicate through the secretion of growth factors, chemokines, and cytokines during tumor progression, and TGF β is unique in its ability to both promote and inhibit tumorigenesis, depending on the cell type it is acting on. Moreover, TGFβ1 could affect various molecular expression, such as P160ROCK, Integrin and Matrix Metalloproteinases,and all of these molecules relate to HCC invasion.