HNF4?-expressing Human Umbilical Cord Mesenchymal Stem Cells Therapies For Tumor Growth And Metastasis After Hepatectomy By SFRP-1

MSC hold promise as target vehicles for the delivery of therapeutic gene products.This potential has been previously demonstrated by their ease of isolation,expansion and genetic modification in vitro and tumor-oriented homing capacity in vivo.HNF4? is a transcription factor that plays a key role in hepatocyte differentiation and the maintenance of hepatic function.Moreover,the overexpression of HNF4? can reportedly effectively suppress the progression of HCC.Here,we overexpressed HNF4? in MSC for the first time to evaluate the effect of MSCHNF4? on the growth of HCC and establish an MSC-based gene therapy for experimental HCC.The data indicate that MSC-HNF4? significantly inhibited tumor growth and metastasis in vitro and in vivo.A complementary antibody analysis showed that MSC-HNF4? secreted significantly more s FRP-1 than normal MSC.Knocking down s FRP-1 expression in MSC-HNF4? substantially diminished their effects on HCC proliferation and invasiveness.We also demonstrate that the s FRP-1-mediated suppression of the progression of HCC requires the down-regulation of ?-catenin via the Wnt signaling pathway and EMT.These findings suggest that s FRP-1 secreted from MSC-HNF4? could be useful in controlling the growth and metastatic recurrence of HCC via the interaction of the Wnt/?-catenin signaling pathway and EMT,which may constitute a new approach for cancer treatment.