title: Mesenchymal stem cells seldomly fuse with hepatocellular carcinoma cells             and are mainly distributed in the tumor stroma in mouse models.
abstract: Mesenchymal stem cells (MSCs) can have an effect on the growth and metastasis of human malignancies, including hepatocellular carcinoma (HCC); however, their mechanisms of action are not yet fully understood. The cell fusion of stem cell derived from bone marrow with other cells has been increasingly emphasized. The purpose of this study was to investigate the distribution of MSCs in mouse models of HCC, as well as the cell fusion between MSCs and HCC cells. We labeled HCC cells and MSCs with green fluorescence protein (GFP), red fluorescence protein (RFP), 4',6-diamidino-2-phenylindole (DAPI) and 5-bromo-2'-deoxyuridine (BrdU). We found that MSCs fused with HCC cells at a low frequency in vitro. MSCs were found to be merged into HCC tissues after intravenous injection, and compared with the mice not injected with MSCs, the MSCs were mainly distributed in the tumor stroma; Following the injection of the MSCs, the tumor stroma was found to have expanded in size, and the rate of pulmonary metastasis in the MSC-injected group was significantly lower (20%) compared to that in the group not injected with MSCs (100%, P=0.01). These data suggest that cell fusion between MSCs and HCC after engraftment is not one of the main mechanisms of action of the MSCs, while stromal differentiation is a major mechanism of action of the MSCs, leading to the inhibition of the pulmonary metastasis of HCC.
authors.affiliation: Liver Cancer Institute and Zhongshan Hospital, Institute of Biomedical Science, Fudan University, Shanghai, PR China.
authors.forename: Guo-Cai
authors.initials: GC
authors.lastname: Li
authors.forename: Qing-Hai
authors.initials: QH
authors.lastname: Ye
authors.forename: Qiong-Zhu
authors.initials: QZ
authors.lastname: Dong
authors.forename: Ning
authors.initials: N
authors.lastname: Ren
authors.forename: Hu-Liang
authors.initials: HL
authors.lastname: Jia
authors.forename: Lun-Xiu
authors.initials: LX
authors.lastname: Qin
mesh_terms: D000818:Animals; D001973:Bromodeoxyuridine; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000556:secondary*; D002454:Cell Differentiation; D002459:Cell Fusion; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D004195:Disease Models, Animal; D049452:Green Fluorescent Proteins; D006801:Humans; D007211:Indoles; D007279:Injections, Subcutaneous; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D049408:Luminescent Agents; D008164:Luminescent Proteins; D008175:Lung Neoplasms / Q000556:secondary*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D000097573:Red Fluorescent Protein
chemical_list: D001973:Bromodeoxyuridine; D049452:Green Fluorescent Proteins; D007211:Indoles; D049408:Luminescent Agents; D008164:Luminescent Proteins; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D000097573:Red Fluorescent Protein; C007293:DAPI