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2016 ; 17
(5
): 558-65
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Overexpression of hepatocyte nuclear factor 4? in human mesenchymal stem cells
suppresses hepatocellular carcinoma development through Wnt/?-catenin signaling
pathway downregulation
#MMPMID27124543
Wu N
; Zhang YL
; Wang HT
; Li DW
; Dai HJ
; Zhang QQ
; Zhang J
; Ma Y
; Xia Q
; Bian JM
; Hang HL
Cancer Biol Ther
2016[May]; 17
(5
): 558-65
PMID27124543
show ga
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 4? (HNF4?) is a dominant transcriptional regulator
of hepatocyte differentiation and hepatocellular carcinogenesis (HCC). (2,3) We
have previously demonstrated that overexpression of HNF4? activates various
hepatic-specific genes and enhances MSC differentiation. (4) However, the extent
that overexpression of HNF4? in MSCs influences HCC progression has yet to be
examined. Here we sought to investigate what effect MSCs overexpressing HNF4?
(MSC-HNF4?) have on human hepatoma cells in vitro and in vivo. Conditioned medium
collected from in vitro MSC-HNF4? cultures significantly inhibited hepatoma cell
growth and metastasis compared with controls. Additionally, nude mice
administered MSC-HNF4? exhibited significantly smaller tumors compared with
controls in vivo. Immunoblot analysis of HCC cells treated with MSC-HNF4?
displayed downregulated ?-catenin, cyclinD1, c-Myc, MMP2 and MMP9. Taken
together, our results demonstrate that MSC-HNF4? inhibits HCC progression by
reducing hepatoma cell growth and metastasis through downregulation of the
Wnt/?-catenin signaling pathway.