Transcriptional repressor snail and metastasis in hepatocellular carcinoma.

BACKGROUND/AIMS: We aimed to elucidate the effect of Snail transcriptional factor on invasion and metastasis and related molecular mechanisms in HCC.

METHODOLOGY

Quantitative RT-PCR was performed to evaluate Snail, E-cadherin and MMP-2 mRNA expressions in HCC tissues from 47 patients as well as the expressions with metastases in these patients. Snail siRNA was transfected into the Snail-over expressing HCC cells and Snail cDNA was transfected into the less Snail-expressed HCC cells. A pseudo metastatic model of HCC in severe combined immunodeficient mice was used to assess the effects of Snail silencing or overexpression on metastasis development.

RESULTS

The relative values of Snail, E-cadherin and MMP-2 mRNA for metastasis tumor was 0.92±0.13, 0.16±0.00 and 0.73±0.10, and for non-metastasis tumor was 0.23±0.01, 0.76±0.002 and 0.24±0.02, respectively. Significant relation was found between Snail and E-cadherin (p=0.013), Snail and MMP-2 (p=0.026). Furthermore, significant relation was revealed between tumor metastasis and Snail (p=0.036), E-cadherin (p=0.048) and MMP-2 mRNA (p=0.037) expression.

CONCLUSIONS

There is an inverse correlation between Snail and E-cadherin expression and a positive correlation between Snail and MMP-2 expression in HCC in vitro and in vivo. Snail downregulates E-cadherin and upregulates MMP-2 expression and promotes invasion in human HCC. Furthermore, Snail inhibition could both upregulate E-cadherin and downregulate MMP-2 expression and inhibit the invasion and metastases in human HCC.