Alpha fetoprotein plays a critical role in promoting metastasis of hepatocellular carcinoma cells

<jats:title>Abstract</jats:title><jats:p>A high level of serum alpha fetoprotein (<jats:styled-content style="fixed-case">AFP</jats:styled-content>) is positively associated with human hepatocellular carcinoma (<jats:styled-content style="fixed-case">HCC</jats:styled-content>) carcinogenesis and metastasis; however, the function of <jats:styled-content style="fixed-case">AFP</jats:styled-content> in <jats:styled-content style="fixed-case">HCC</jats:styled-content> metastasis is unknown. This study has explored the effects of <jats:styled-content style="fixed-case">AFP</jats:styled-content> on regulating metastatic and invasive capacity of human <jats:styled-content style="fixed-case">HCC</jats:styled-content> cells. Forty‐seven clinical patients' liver samples were collected and diagnosed; <jats:styled-content style="fixed-case">HCC</jats:styled-content> cells line, Bel 7402 cells (<jats:styled-content style="fixed-case">AFP</jats:styled-content>‐producing) and liver cancer cell line cells (non‐<jats:styled-content style="fixed-case">AFP</jats:styled-content>‐producing) were selected to analyse the role of <jats:styled-content style="fixed-case">AFP</jats:styled-content> in the metastasis of <jats:styled-content style="fixed-case">HCC</jats:styled-content> cells. The results indicated that high serum concentration of <jats:styled-content style="fixed-case">AFP</jats:styled-content> was positively correlated with <jats:styled-content style="fixed-case">HCC</jats:styled-content> intrahepatic, lymph nodes and lung metastasis. Repressed expression of <jats:styled-content style="fixed-case">AFP</jats:styled-content> significantly inhibited the capability of migration and invasion of Bel 7402 cells, expression of keratin 19 (K19), epithelial cell adhesion molecule (Ep<jats:styled-content style="fixed-case">CAM</jats:styled-content>), matrix metalloproteinase 2/9 (<jats:styled-content style="fixed-case">MMP</jats:styled-content>2/9) and <jats:styled-content style="fixed-case">CXC</jats:styled-content> chemokine receptor 4 (<jats:styled-content style="fixed-case">CXCR</jats:styled-content>4) were also down‐regulated in Bel 7402 cells; migration and invasion, expression of K19, Ep<jats:styled-content style="fixed-case">CAM</jats:styled-content>,<jats:styled-content style="fixed-case"> MMP</jats:styled-content>2/9 and <jats:styled-content style="fixed-case">CXCR</jats:styled-content>4 were significantly enhanced when <jats:styled-content style="fixed-case">HLE</jats:styled-content> cells were transfected with <jats:styled-content style="fixed-case">AFP</jats:styled-content>‐expressed vector. The results demonstrated that <jats:styled-content style="fixed-case">AFP</jats:styled-content> plays a critical role in promoting metastasis of <jats:styled-content style="fixed-case">HCC</jats:styled-content>;<jats:styled-content style="fixed-case"> AFP</jats:styled-content> promoted <jats:styled-content style="fixed-case">HCC</jats:styled-content> cell invasion and metastasis <jats:italic>via</jats:italic> up‐regulating expression of metastasis‐related proteins. Thus, <jats:styled-content style="fixed-case">AFP</jats:styled-content> may be used as a novel therapeutic target for treating <jats:styled-content style="fixed-case">HCC</jats:styled-content> patients.</jats:p>