4.5 Article

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

Journal

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
Volume 20, Issue 3, Pages 549-558

Publisher

WILEY
DOI: 10.1111/jcmm.12745

Keywords

alpha fetoprotein; liver cancer cells metastasis; therapeutic target

Funding

  1. National Natural Science Foundation of China [81560450, 31560243, 81360307, 81260306, 81160261, 31060164, 30960153]
  2. Key Program of Science and Technology, Ministry of Education of China [211146]
  3. Key Projects of Science and Technology, Hainan Province [ZDXM 20110038]
  4. New Century Excellent Talents in China [NCET-10-0124]
  5. Natural Science Foundation of Hainan Province [309034, 310044, 811208, 814293]
  6. fund of Hainan Province Social Development [2015SF03]

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A high level of serum alpha fetoprotein (AFP) is positively associated with human hepatocellular carcinoma (HCC) carcinogenesis and metastasis; however, the function of AFP in HCC metastasis is unknown. This study has explored the effects of AFP on regulating metastatic and invasive capacity of human HCC cells. Forty-seven clinical patients' liver samples were collected and diagnosed; HCC cells line, Bel 7402 cells (AFP-producing) and liver cancer cell line cells (non-AFP-producing) were selected to analyse the role of AFP in the metastasis of HCC cells. The results indicated that high serum concentration of AFP was positively correlated with HCC intrahepatic, lymph nodes and lung metastasis. Repressed expression of AFP significantly inhibited the capability of migration and invasion of Bel 7402 cells, expression of keratin 19 (K19), epithelial cell adhesion molecule (EpCAM), matrix metalloproteinase 2/9 (MMP2/9) and CXC chemokine receptor 4 (CXCR4) were also down-regulated in Bel 7402 cells; migration and invasion, expression of K19, EpCAM, MMP2/9 and CXCR4 were significantly enhanced when HLE cells were transfected with AFP-expressed vector. The results demonstrated that AFP plays a critical role in promoting metastasis of HCC; AFP promoted HCC cell invasion and metastasis via up-regulating expression of metastasis-related proteins. Thus, AFP may be used as a novel therapeutic target for treating HCC patients.

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