Abstract
BackgroundThe discovery of cancer stem cells and tumor heterogeneity prompted the exploration of additional mechanisms aside from genetic mutations for carcinogenesis and cancer progression. The aim of the present study was to investigate the effect of cell fusion between mesenchymal stem cells and the gastric epithelial cells in tumorigenesis.MethodsCell fusion between cord blood mesenchymal stem cells and human gastric epithelial cells was performed in vitro. Cell scratch and transwell assays were performed to determine migration and invasion abilities of the hybrids. The expressions of epithelial-mesenchymal transition-related proteins and genes were analyzed by immunocytochemistry and real time quantitative PCR. Tumorigenesis of the hybrids was evaluated through in vivo inoculation in nude mice.ResultsHybrids expressed the phenotypes of both donor cells. Aneuploidy was observed in 84.1% of cells. The hybrids showed increased proliferation, migration and invasion abilities compared with the parental cells. In addition, the expression of N-cadherin and vimentin in the hybrids was significantly higher than that of the epithelial cells, and the mRNA expression of the epithelial-mesenchymal transition-related genes, Twist and Slug, in the hybrids was also increased compared with that of the parental epithelial cells. Furthermore, the hybrids formed masses of epithelial origin with glandular structures in BALB/c nude mice.ConclusionsThese findings suggest that cell fusion between gastric epithelial cells and mesenchymal stem cells may result in epithelial to mesenchymal transition and malignant transformation.
Highlights
The discovery of cancer stem cells and tumor heterogeneity prompted the exploration of additional mechanisms aside from genetic mutations for carcinogenesis and cancer progression
The results revealed that the hybrids of GES-1 and cord matrix-derived mesenchymal stem cells (CM-Mesenchymal stem cells (MSCs)) undergo epithelialmesenchymal transition (EMT), indicated by the increased capability of proliferation, migration and invasion, and the expression of EMT-related genes and tumor formation in nude mice
Migration and invasive ability of the hybrids significantly increased in vitro and the hybrids were able to form subcutaneous mass of epithelial origin in vivo. These results indicate that bone marrow-derived stem cells (BMDSCs) acquire an epithelial phenotype through cell fusion, and that cell fusion may be the mechanism for gastric epithelial cells to acquire metastatic ability
Summary
The discovery of cancer stem cells and tumor heterogeneity prompted the exploration of additional mechanisms aside from genetic mutations for carcinogenesis and cancer progression. The aim of the present study was to investigate the effect of cell fusion between mesenchymal stem cells and the gastric epithelial cells in tumorigenesis. The potential pathological consequence of fusion between bone marrow-derived stem cells (BMDSCs) and epithelial cells remains to be unknown. We previously hypothesized that fusion between an “altered” pre-malignant cell and a bone marrow-derived stem cell results in malignant transformation of the hybrid progeny cells [2]. The “altered” cells are defined as any cells with genetic or epigenetic changes sufficient to change the normal differentiation pathway of BMDSCs after fusion. We fused immortalized GES-1 cells with cord matrix-derived mesenchymal stem cells (CM-MSCs). The results revealed that the hybrids of GES-1 and CM-MSCs undergo epithelialmesenchymal transition (EMT), indicated by the increased capability of proliferation, migration and invasion, and the expression of EMT-related genes and tumor formation in nude mice
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