Limits...
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.

Show MeSH

Related in: MedlinePlus

DNA ploidy analysis and cell scratch assays. (A) DNA ploidy analysis was performed on the parental and progeny cells. GES-1 and CM-MSCs were diploid. The majority of hybrids were aneuploidy cells (84.10%) (Figure 2A). The remainders were diploid (12.09%) and polyploid (3.81%). (B) Cell scratch results showed that hybrids had stronger migration ability than GES-1 cells. At 24 h, no significant difference was observed, but at 48 h, hybrids migrated toward the center of the scratch and almost filled the area. By 72 h, hybrids migrated toward the center and filled the area. CM-MSCs mirgrated fastest and filled the scratch at 48 h. Magnification: 100×, Scale bar 100 μm. Data are a representative of three experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig2: DNA ploidy analysis and cell scratch assays. (A) DNA ploidy analysis was performed on the parental and progeny cells. GES-1 and CM-MSCs were diploid. The majority of hybrids were aneuploidy cells (84.10%) (Figure 2A). The remainders were diploid (12.09%) and polyploid (3.81%). (B) Cell scratch results showed that hybrids had stronger migration ability than GES-1 cells. At 24 h, no significant difference was observed, but at 48 h, hybrids migrated toward the center of the scratch and almost filled the area. By 72 h, hybrids migrated toward the center and filled the area. CM-MSCs mirgrated fastest and filled the scratch at 48 h. Magnification: 100×, Scale bar 100 μm. Data are a representative of three experiments.

Mentions: DNA ploidy analysis was performed on the parental and progeny cells. GES-1 and CM-MSCs were diploid. The majority of hybrids were aneuploidy cells (84.10%) (Figure 2A). The remainders were diploid (12.09%) and polyploid (3.81%), a characteristic of tumor cells. In the cell scratch assay (Figure 2B) the hybrids had greater migration ability than GES-1. At 24 h, no significant difference was observed, but at 48 h the hybrids began to migrate toward the center of the scratch. By 72 h, the hybrids filled the scratch, while GES-1 cells migrated toward the center of the scratch but did not fill the area. CM-MSCs filled the scratch at 48 h. Furthermore, in the transwell migration assay, GES-1 (31.57 ± 15.55 cells/field) (Figure 3A), CM-MSCs (30.14 ± 18.75 cells/field) (Figure 3B), and hybrids (112.3 ± 10.36 cells/field) (Figure 3C) crossed the microporous membrane at 24 h, but in the transwell invasive assay only the hybrids cells (102.3 ± 24.33 cells/field) (Figure 3D) were able to penetrate the Matrigel coating and cross the microporous membrane. The numbers of migrated cells are significant difference as comparing hybrids to GES-1 and CM-MSCs (Figure 3E). These results indicate that fusion of GES-1 with CM-MSCs not only increase the migration ability, but also increase the invasive ability of the hybrids. MTT results show that the hybrids proliferate at a faster rate than GES-1 and CM-MSCs (Figure 3F). No significant difference between proliferation rates was observed on day 1 and 2, but the proliferation rate of the hybrids significantly increased at day 3 and day 4.Figure 2


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)

DNA ploidy analysis and cell scratch assays. (A) DNA ploidy analysis was performed on the parental and progeny cells. GES-1 and CM-MSCs were diploid. The majority of hybrids were aneuploidy cells (84.10%) (Figure 2A). The remainders were diploid (12.09%) and polyploid (3.81%). (B) Cell scratch results showed that hybrids had stronger migration ability than GES-1 cells. At 24 h, no significant difference was observed, but at 48 h, hybrids migrated toward the center of the scratch and almost filled the area. By 72 h, hybrids migrated toward the center and filled the area. CM-MSCs mirgrated fastest and filled the scratch at 48 h. Magnification: 100×, Scale bar 100 μm. Data are a representative of three experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig2: DNA ploidy analysis and cell scratch assays. (A) DNA ploidy analysis was performed on the parental and progeny cells. GES-1 and CM-MSCs were diploid. The majority of hybrids were aneuploidy cells (84.10%) (Figure 2A). The remainders were diploid (12.09%) and polyploid (3.81%). (B) Cell scratch results showed that hybrids had stronger migration ability than GES-1 cells. At 24 h, no significant difference was observed, but at 48 h, hybrids migrated toward the center of the scratch and almost filled the area. By 72 h, hybrids migrated toward the center and filled the area. CM-MSCs mirgrated fastest and filled the scratch at 48 h. Magnification: 100×, Scale bar 100 μm. Data are a representative of three experiments.
Mentions: DNA ploidy analysis was performed on the parental and progeny cells. GES-1 and CM-MSCs were diploid. The majority of hybrids were aneuploidy cells (84.10%) (Figure 2A). The remainders were diploid (12.09%) and polyploid (3.81%), a characteristic of tumor cells. In the cell scratch assay (Figure 2B) the hybrids had greater migration ability than GES-1. At 24 h, no significant difference was observed, but at 48 h the hybrids began to migrate toward the center of the scratch. By 72 h, the hybrids filled the scratch, while GES-1 cells migrated toward the center of the scratch but did not fill the area. CM-MSCs filled the scratch at 48 h. Furthermore, in the transwell migration assay, GES-1 (31.57 ± 15.55 cells/field) (Figure 3A), CM-MSCs (30.14 ± 18.75 cells/field) (Figure 3B), and hybrids (112.3 ± 10.36 cells/field) (Figure 3C) crossed the microporous membrane at 24 h, but in the transwell invasive assay only the hybrids cells (102.3 ± 24.33 cells/field) (Figure 3D) were able to penetrate the Matrigel coating and cross the microporous membrane. The numbers of migrated cells are significant difference as comparing hybrids to GES-1 and CM-MSCs (Figure 3E). These results indicate that fusion of GES-1 with CM-MSCs not only increase the migration ability, but also increase the invasive ability of the hybrids. MTT results show that the hybrids proliferate at a faster rate than GES-1 and CM-MSCs (Figure 3F). No significant difference between proliferation rates was observed on day 1 and 2, but the proliferation rate of the hybrids significantly increased at day 3 and day 4.Figure 2

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