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Cell fusion between gastric epithelial cells and mesenchymal stem cells results in epithelial-to-mesenchymal transition and malignant transformation.

He X, Li B, Shao Y, Zhao N, Hsu Y, Zhang Z, Zhu L - BMC Cancer (2015)

Bottom Line: 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.Aneuploidy was observed in 84.1% of cells.These findings suggest that cell fusion between gastric epithelial cells and mesenchymal stem cells may result in epithelial to mesenchymal transition and malignant transformation.

View Article: PubMed Central - PubMed

Affiliation: Department of General Surgery, Tianjin General Surgery Institute, Tianjin Medical University General Hospital, Tianjin, 300052, China. humphreyhe@163.com.

ABSTRACT

Background: 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.

Methods: Cell 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.

Results: Hybrids 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.

Conclusions: These findings suggest that cell fusion between gastric epithelial cells and mesenchymal stem cells may result in epithelial to mesenchymal transition and malignant transformation.

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Expression of EMT-related genes in hybrids. Cells grown on coverslips were fixed and stained for the expression of E-cadherin, N-cadherin and vimentin. Magnification 200×. No E-cadherin expression was detected in all cells types (panel A, GES-1; panel D, CM-MSCs; panel G, hybrids); N-cadherin expression was weak in GES-1 cells (panel B), while CM-MSCs had strong expression (panel E). The hybrids had moderate N-cadherin expression (panel H). GES-1 cells expressed vimentin weakly (panel C), while both CM-MSCs (panel F) and hybrids (panel I) had strong expression. Twist and Slug mRNA transcription were analyzed by quantitative RT-PCR. Compared with GES-1 cells, the mRNA expressions of Twist in CM-MSCs and fusion cells were upregulated by (15.2 ± 8.7)- and (8.7 ± 2.1)-fold, respectively; similarly, the mRNA expressions of Slug in CM-MSCs and fusion cells were upregulated by (27.8 ± 4.2)- and (9.2 ± 1.8)-fold, respectively (p < 0.05) (panel J). Means ± SD of three representative results are shown.
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Fig4: Expression of EMT-related genes in hybrids. Cells grown on coverslips were fixed and stained for the expression of E-cadherin, N-cadherin and vimentin. Magnification 200×. No E-cadherin expression was detected in all cells types (panel A, GES-1; panel D, CM-MSCs; panel G, hybrids); N-cadherin expression was weak in GES-1 cells (panel B), while CM-MSCs had strong expression (panel E). The hybrids had moderate N-cadherin expression (panel H). GES-1 cells expressed vimentin weakly (panel C), while both CM-MSCs (panel F) and hybrids (panel I) had strong expression. Twist and Slug mRNA transcription were analyzed by quantitative RT-PCR. Compared with GES-1 cells, the mRNA expressions of Twist in CM-MSCs and fusion cells were upregulated by (15.2 ± 8.7)- and (8.7 ± 2.1)-fold, respectively; similarly, the mRNA expressions of Slug in CM-MSCs and fusion cells were upregulated by (27.8 ± 4.2)- and (9.2 ± 1.8)-fold, respectively (p < 0.05) (panel J). Means ± SD of three representative results are shown.

Mentions: EMT is characterized by the loss of epithelial marker E-cadherin and expression of mesenchymal markers including N-cadherin and vimentin [8]. Immunocytochemistry was performed to evaluate the expressions of E-cadherin, N-cadherin and vimentin here. GES-1, CM-MSCs and hybrids were all negative for E-cadherin (Figure 4A, D, G). GES-1 cells were weak for N-cadherin expression, CM-MSCs were strongly positive, and the hybrids had moderate expression (Figure 4B, E, H). For vimentin expression, GES-1 was weakly positive, and both CM-MSCs and the hybrids exhibited strong expression (Figure 4C, F, I). Real-time PCR was performed to measure the transcription of the EMT-related genes Twist and Slug in GES-1, CM-MSCs and fusion cells. Compared with GES-1, the mRNA expressions of Twist in CM-MSCs and fusion cells were upregulated by (15.2 ± 8.7)- and (8.7 ± 2.1)-fold, respectively. Similarly, the mRNA expressions of Slug in CM-MSCs and fusion cells were upregulated by (27.8 ± 4.2)- and (9.2 ± 1.8)-fold, respectively (p < 0.05) (Figure 4J).Figure 4


Cell fusion between gastric epithelial cells and mesenchymal stem cells results in epithelial-to-mesenchymal transition and malignant transformation.

He X, Li B, Shao Y, Zhao N, Hsu Y, Zhang Z, Zhu L - BMC Cancer (2015)

Expression of EMT-related genes in hybrids. Cells grown on coverslips were fixed and stained for the expression of E-cadherin, N-cadherin and vimentin. Magnification 200×. No E-cadherin expression was detected in all cells types (panel A, GES-1; panel D, CM-MSCs; panel G, hybrids); N-cadherin expression was weak in GES-1 cells (panel B), while CM-MSCs had strong expression (panel E). The hybrids had moderate N-cadherin expression (panel H). GES-1 cells expressed vimentin weakly (panel C), while both CM-MSCs (panel F) and hybrids (panel I) had strong expression. Twist and Slug mRNA transcription were analyzed by quantitative RT-PCR. Compared with GES-1 cells, the mRNA expressions of Twist in CM-MSCs and fusion cells were upregulated by (15.2 ± 8.7)- and (8.7 ± 2.1)-fold, respectively; similarly, the mRNA expressions of Slug in CM-MSCs and fusion cells were upregulated by (27.8 ± 4.2)- and (9.2 ± 1.8)-fold, respectively (p < 0.05) (panel J). Means ± SD of three representative results are shown.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Fig4: Expression of EMT-related genes in hybrids. Cells grown on coverslips were fixed and stained for the expression of E-cadherin, N-cadherin and vimentin. Magnification 200×. No E-cadherin expression was detected in all cells types (panel A, GES-1; panel D, CM-MSCs; panel G, hybrids); N-cadherin expression was weak in GES-1 cells (panel B), while CM-MSCs had strong expression (panel E). The hybrids had moderate N-cadherin expression (panel H). GES-1 cells expressed vimentin weakly (panel C), while both CM-MSCs (panel F) and hybrids (panel I) had strong expression. Twist and Slug mRNA transcription were analyzed by quantitative RT-PCR. Compared with GES-1 cells, the mRNA expressions of Twist in CM-MSCs and fusion cells were upregulated by (15.2 ± 8.7)- and (8.7 ± 2.1)-fold, respectively; similarly, the mRNA expressions of Slug in CM-MSCs and fusion cells were upregulated by (27.8 ± 4.2)- and (9.2 ± 1.8)-fold, respectively (p < 0.05) (panel J). Means ± SD of three representative results are shown.
Mentions: EMT is characterized by the loss of epithelial marker E-cadherin and expression of mesenchymal markers including N-cadherin and vimentin [8]. Immunocytochemistry was performed to evaluate the expressions of E-cadherin, N-cadherin and vimentin here. GES-1, CM-MSCs and hybrids were all negative for E-cadherin (Figure 4A, D, G). GES-1 cells were weak for N-cadherin expression, CM-MSCs were strongly positive, and the hybrids had moderate expression (Figure 4B, E, H). For vimentin expression, GES-1 was weakly positive, and both CM-MSCs and the hybrids exhibited strong expression (Figure 4C, F, I). Real-time PCR was performed to measure the transcription of the EMT-related genes Twist and Slug in GES-1, CM-MSCs and fusion cells. Compared with GES-1, the mRNA expressions of Twist in CM-MSCs and fusion cells were upregulated by (15.2 ± 8.7)- and (8.7 ± 2.1)-fold, respectively. Similarly, the mRNA expressions of Slug in CM-MSCs and fusion cells were upregulated by (27.8 ± 4.2)- and (9.2 ± 1.8)-fold, respectively (p < 0.05) (Figure 4J).Figure 4

Bottom Line: 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.Aneuploidy was observed in 84.1% of cells.These findings suggest that cell fusion between gastric epithelial cells and mesenchymal stem cells may result in epithelial to mesenchymal transition and malignant transformation.

View Article: PubMed Central - PubMed

Affiliation: Department of General Surgery, Tianjin General Surgery Institute, Tianjin Medical University General Hospital, Tianjin, 300052, China. humphreyhe@163.com.

ABSTRACT

Background: 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.

Methods: Cell 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.

Results: Hybrids 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.

Conclusions: These findings suggest that cell fusion between gastric epithelial cells and mesenchymal stem cells may result in epithelial to mesenchymal transition and malignant transformation.

Show MeSH
Related in: MedlinePlus