Fusion of HepG2 cells with mesenchymal stem cells increases cancer‑associated and malignant properties: An in vivo metastasis model

Li,Hong; Feng,Zhenqing; Tsang,Tom  C.; Tang,Tian; Jia,Xiaoqin; He,Xianghui; Pennington,Michael  E.; Badowski,Michael  S.; Liu,Anna  K.M.; Chen,Deyu; Harris,David  T.; Martinez,Jesse; Meade-Tollin,Linda  C.

doi:10.3892/or.2014.3264

Fusion of HepG2 cells with mesenchymal stem cells increases cancer‑associated and malignant properties: An in vivo metastasis model

Authors:
- Hong Li
- Zhenqing Feng
- Tom C. Tsang
- Tian Tang
- Xiaoqin Jia
- Xianghui He
- Michael E. Pennington
- Michael S. Badowski
- Anna K.M. Liu
- Deyu Chen
- David T. Harris
- Jesse Martinez
- Linda C. Meade-Tollin
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Affiliations: Department of Pathology, Binzhou Medical University Hospital, Binzhou 256603, P.R. China, Key Laboratory of Antibody Technique of the Ministry of Health, Department of Pathology, Nanjing Medical University, Nanjing 210029, P.R. China, Department of General Surgery, Tianjin General Surgery Institute, General Hospital of Tianjin Medical University, Tianjin 300052, P.R. China, Cure Cancer Worldwide Corporation, Tucson, AZ 85728-5833, USA, Department of Immunobiology, University of Arizona, Tucson, AZ 85724, USA, Department of Oncology, The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, P.R. China, Arizona Cancer Center, University of Arizona, Tucson, AZ 85721, USA
Published online on: June 13, 2014 https://doi.org/10.3892/or.2014.3264
Pages: 539-547

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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.

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