Details

Autor(en) / Beteiligte

• Wu, Ning
• Zhang, Yu-Ling
• Wang, Hai-Tian
• Li, Da-Wei
• Dai, Hui-Juan
• Zhang, Qi-Qi
• Zhang, Jiang
• Ma, Yong
• Xia, Qiang
• Bian, Jian-Min
• Hang, Hua-Lian

Titel

Overexpression of hepatocyte nuclear factor 4α in human mesenchymal stem cells suppresses hepatocellular carcinoma development through Wnt/β-catenin signaling pathway downregulation

Ist Teil von

• Cancer biology & therapy, 2016-05, Vol.17 (5), p.558-565

Ort / Verlag

United States: Taylor & Francis

Erscheinungsjahr

2016

Link zum Volltext

Quelle

Taylor & Francis Journals Auto-Holdings Collection

Beschreibungen/Notizen

• Mesenchymal stem cells (MSCs) hold promise as cellular vehicles for the delivery of therapeutic gene products because they can be isolated, expanded, and genetically modified in vitro and possess tumor-oriented homing capacity in vivo. 1 Hepatocyte nuclear factor 4α (HNF4α) is a dominant transcriptional regulator of hepatocyte differentiation and hepatocellular carcinogenesis (HCC). 2,3 We have previously demonstrated that overexpression of HNF4α activates various hepatic-specific genes and enhances MSC differentiation. 4 However, the extent that overexpression of HNF4α in MSCs influences HCC progression has yet to be examined. Here we sought to investigate what effect MSCs overexpressing HNF4α (MSC-HNF4α) have on human hepatoma cells in vitro and in vivo. Conditioned medium collected from in vitro MSC-HNF4α cultures significantly inhibited hepatoma cell growth and metastasis compared with controls. Additionally, nude mice administered MSC-HNF4α exhibited significantly smaller tumors compared with controls in vivo. Immunoblot analysis of HCC cells treated with MSC-HNF4α displayed downregulated β-catenin, cyclinD1, c-Myc, MMP2 and MMP9. Taken together, our results demonstrate that MSC-HNF4α inhibits HCC progression by reducing hepatoma cell growth and metastasis through downregulation of the Wnt/β-catenin signaling pathway.