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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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Related in: MedlinePlus

GES-1 versus hybrids. GES-1 (A) and CM-MSCs (C) were stained using PKH26 (B) and CFSE (D) separately. At day 1 after in vivo cell fusion and cell sorting, most cells expressed both PKH26 and CFSE (E–G), and the hybrids began growing colonies at day 5 (H). H&E staining showed that the morphologies of GES-1 (I) and fusion cells (J) were oval, spindle or polygonal, and CK-18 IF results showed that CK-18 was expressed in the cytoplasm in both GES-1 (K) and fusion cells (L). Magnification: 400×, Scale bar A-J = 25 μm; K-L = 20 μm.
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Fig1: GES-1 versus hybrids. GES-1 (A) and CM-MSCs (C) were stained using PKH26 (B) and CFSE (D) separately. At day 1 after in vivo cell fusion and cell sorting, most cells expressed both PKH26 and CFSE (E–G), and the hybrids began growing colonies at day 5 (H). H&E staining showed that the morphologies of GES-1 (I) and fusion cells (J) were oval, spindle or polygonal, and CK-18 IF results showed that CK-18 was expressed in the cytoplasm in both GES-1 (K) and fusion cells (L). Magnification: 400×, Scale bar A-J = 25 μm; K-L = 20 μm.

Mentions: CM-MSCs were successfully cultured and collected. Expression of the most recognized surface antigen of CM-MSCs, including HLA-ABC, SH2 (CD105) and SH4 (CD73), was analyzed by flow cytometry, with 99.69%, 99.74%, and 99.73% positivity, respectively. Expressions of HLA-DR, CD45, and CD34 were also analyzed to assess hematopoietic stem cell contamination; expressions of these antigens were 0.01%, 1.59%, and 0.03% respectively. After GES-1 (Figure 1A, B) and CM-MSCs (Figure 1C, D) were labeled with PKH-26 and CFSE, in vitro cell fusion between GES-1 and CM-MSCs was performed.Figure 1


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)

GES-1 versus hybrids. GES-1 (A) and CM-MSCs (C) were stained using PKH26 (B) and CFSE (D) separately. At day 1 after in vivo cell fusion and cell sorting, most cells expressed both PKH26 and CFSE (E–G), and the hybrids began growing colonies at day 5 (H). H&E staining showed that the morphologies of GES-1 (I) and fusion cells (J) were oval, spindle or polygonal, and CK-18 IF results showed that CK-18 was expressed in the cytoplasm in both GES-1 (K) and fusion cells (L). Magnification: 400×, Scale bar A-J = 25 μm; K-L = 20 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4318156&req=5

Fig1: GES-1 versus hybrids. GES-1 (A) and CM-MSCs (C) were stained using PKH26 (B) and CFSE (D) separately. At day 1 after in vivo cell fusion and cell sorting, most cells expressed both PKH26 and CFSE (E–G), and the hybrids began growing colonies at day 5 (H). H&E staining showed that the morphologies of GES-1 (I) and fusion cells (J) were oval, spindle or polygonal, and CK-18 IF results showed that CK-18 was expressed in the cytoplasm in both GES-1 (K) and fusion cells (L). Magnification: 400×, Scale bar A-J = 25 μm; K-L = 20 μm.
Mentions: CM-MSCs were successfully cultured and collected. Expression of the most recognized surface antigen of CM-MSCs, including HLA-ABC, SH2 (CD105) and SH4 (CD73), was analyzed by flow cytometry, with 99.69%, 99.74%, and 99.73% positivity, respectively. Expressions of HLA-DR, CD45, and CD34 were also analyzed to assess hematopoietic stem cell contamination; expressions of these antigens were 0.01%, 1.59%, and 0.03% respectively. After GES-1 (Figure 1A, B) and CM-MSCs (Figure 1C, D) were labeled with PKH-26 and CFSE, in vitro cell fusion between GES-1 and CM-MSCs was performed.Figure 1

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