FOXP3 expression in FOXP3⁺ tumor cells promotes hepatocellular cells metastasis

Forkhead transcription factor 3 (FOXP3) is a key molecule for the development of regulatory T cell. Recent studies showed that FOXP3 was also expressed in tumor cells. This study is designed to identify the expression of FOXP3 and its pathogenesis in hepatocellular carcinoma (HCC).

Through immunohistochemistry, RNA extraction and Real-Time Quantitative PCR, western blot analysis, transwell cell migration assay and invasion assays, and in vivo experiment, we detected FOXP3 expression in HCC and analyzed the expression of tumor metastasis-related genes in HCC cells using female BALB/c-Nude mice.

The results showed that FOXP3 was expressed in partial HCC tissues samples and cell lines. The distant metastasis rate was remarkably higher in the FOXP3 positive HCCs than that in the negative group. The positive rate of FOXP3 expression in the metastatic HCC was higher than that in primary HCC, and the expression level of FOXP3 was found to increase as the enhancement in the metastatic potential of the cell lines. Furthermore, in HCC cell lines, FOXP3 overexpression can promote the cell metastasis and invasion by regulating MMP-1. The in vivo experiment showed that the proliferation ability of HepG2 cells in nude mice increased significantly after FOXP3 was overexpressed, and the incidence rate of lung metastasis in MHCC97L cells was significantly deceased after knocking down the FOXP3 expression.

Our findings support that partial HCC tissues and cell lines expressing FOXP3 can promote the metastasis by regulating MMP-1.