title: Fusion of HepG2 cells with mesenchymal stem cells increases cancer‑associated and malignant properties: an in vivo metastasis model.
abstract: In the present study, we have tested the hypothesis that fusion between an altered cell and a mesenchymal stem cell produces a hybrid cell with enhanced characteristics associated with metastatic cancer cells, and we have developed a flexible model for investigating the mechanisms of metastasis. Human HepG2 cells with low metastatic potential were induced to fuse with rat bone marrow mesenchymal stem cells, and the progeny were compared with the parental cells for possession of enhanced in vitro and in vivo characteristics of malignant cells. Compared to the parental cells, the fused cells exhibited enhanced expression of E-cadherin, vimentin, Twist, Snail, matrix metalloproteinase 2 and 9 activities, aneuploidy and enhanced in vitro invasion and migration. In an in vivo xenograft assay, the fused cells generated increased numbers of metastatic liver and lung lesions. This model system is a flexible tool for investigation of the mechanisms of stem cell fusion in carcinogenesis and metastasis and for the discovery of new therapeutic targets to inhibit metastasis.
authors.affiliation: Department of Pathology, Binzhou Medical University Hospital, Binzhou 256603, P.R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.affiliation: Key Laboratory of Antibody Technique of the Ministry of Health, Department of Pathology, Nanjing Medical University, Nanjing 210029, P.R. China.
authors.forename: Zhenqing
authors.initials: Z
authors.lastname: Feng
authors.affiliation: Key Laboratory of Antibody Technique of the Ministry of Health, Department of Pathology, Nanjing Medical University, Nanjing 210029, P.R. China.
authors.forename: Tom C
authors.initials: TC
authors.lastname: Tsang
authors.affiliation: Key Laboratory of Antibody Technique of the Ministry of Health, Department of Pathology, Nanjing Medical University, Nanjing 210029, P.R. China.
authors.forename: Tian
authors.initials: T
authors.lastname: Tang
authors.affiliation: Key Laboratory of Antibody Technique of the Ministry of Health, Department of Pathology, Nanjing Medical University, Nanjing 210029, P.R. China.
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Jia
authors.affiliation: Department of General Surgery, Tianjin General Surgery Institute, General Hospital of Tianjin Medical University, Tianjin 300052, P.R. China.
authors.forename: Xianghui
authors.initials: X
authors.lastname: He
authors.affiliation: Cure Cancer Worldwide Corporation, Tucson, AZ 85728-5833, USA.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Pennington
authors.affiliation: Department of Immunobiology, University of Arizona, Tucson, AZ 85724, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Badowski
authors.affiliation: Department of Immunobiology, University of Arizona, Tucson, AZ 85724, USA.
authors.forename: Anna K M
authors.initials: AK
authors.lastname: Liu
authors.affiliation: Department of Oncology, The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, P.R. China.
authors.forename: Deyu
authors.initials: D
authors.lastname: Chen
authors.affiliation: Arizona Cancer Center, University of Arizona, Tucson, AZ 85721, USA.
authors.forename: David T
authors.initials: DT
authors.lastname: Harris
authors.affiliation: Arizona Cancer Center, University of Arizona, Tucson, AZ 85721, USA.
authors.forename: Jesse
authors.initials: J
authors.lastname: Martinez
authors.affiliation: Cure Cancer Worldwide Corporation, Tucson, AZ 85728-5833, USA.
authors.forename: Linda C
authors.initials: LC
authors.lastname: Meade-Tollin
mesh_terms: D000782:Aneuploidy; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002459:Cell Fusion; D002465:Cell Movement; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology* / Q000556:secondary; D008175:Lung Neoplasms / Q000473:pathology* / Q000556:secondary; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D051381:Rats; D017207:Rats, Sprague-Dawley