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

He, Xianghui; Li, Baosong; Shao, Yang; Zhao, Ning; Hsu, Yi-Ling; Zhang, Zhixiang; Zhu, Lingjun

doi:10.1186/s12885-015-1027-1

Cited by 40 publications

(45 citation statements)

References 19 publications

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“…Of interest were findings indicating an increased CXCR4 expression in hybrid cells, which may be related to metastatic spreading [ 31 ]. This would be in view with recent data indicating that fusion between gastric epithelial cells and mesenchymal stem cells resulted in epithelial-to-mesenchymal and malignant transformation of the hybrid cells [ 32 ].…”

Section: Introductionsupporting

confidence: 82%

Lipopolysaccharide (LPS) Promotes Apoptosis in Human Breast Epithelial × Breast Cancer Hybrids, but Not in Parental Cells

et al. 2016

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Toll-like receptors (TLRs) belong to the group of pathogen recognition receptors known to play a crucial role in the innate immune system. In cancer, TLR expression is still debated controversially due to contradictory results reporting that both induction of apoptosis as well as tumor progression could depend on TLR signaling, whereby recent data rather indicate a pro-tumorigenic effect. The biological phenomenon of cell fusion has been associated with cancer progression due to findings revealing that fusion-derived hybrid cells could exhibit properties like an increased metastatogenic capacity and an increased drug resistance. Thus, M13MDA435 hybrid cell lines, which derived from spontaneous fusion events between human M13SV1-EGFP-Neo breast epithelial cells and human MDA-MB-435-Hyg breast cancer cells, were investigated. Cultivation of cells in the presence of the TLR4 ligand LPS potently induced apoptosis in all hybrid clones, but not in parental cells, which was most likely attributed to differential kinetics of the TLR4 signal transduction cascade. Activation of this pathway concomitant with NF-κB nuclear translocation and TNF-α expression was solely observed in hybrid cells. However, induction of LPS mediated apoptosis was not TNF-α dependent since TNF-α neutralization was not correlated to a decreased amount of dead cells. In addition to TNF-α, LPS also caused IFN-β expression in hybrid clones 1 and 3. Interestingly, hybrid clones differ in the mode of LPS induced apoptosis. While neutralization of IFN-β was sufficient to impair the LPS induced apoptosis in M13MDA435-1 and -3 hybrids, the amount of apoptotic M13MDA435-2 and -4 hybrid cells remained unchanged in the presence of neutralizing IFN-β antibodies. In summary, the fusion of non-LPS susceptible parental human breast epithelial cells and human breast cancer cells gave rise to LPS susceptible hybrid cells, which is in view with the cell fusion hypothesis that hybrid cells could exhibit novel properties.

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Section: Introductionsupporting

confidence: 82%

Lipopolysaccharide (LPS) Promotes Apoptosis in Human Breast Epithelial × Breast Cancer Hybrids, but Not in Parental Cells

et al. 2016

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“…MSCs may be recruited to the Helicobacter Pylori-infected gastric mucosa where they fuse with existing neoplastic and pre-neoplastic epithelial cells. Fusion of MSC with gastric epithelial cells increases invasion and metastasis of gastric cancer [ 32 ]. The spontaneous formation of BM-MSCs and lung/breast cancer hybrids acquire the tumorigenic and metastatic properties as well as mesenchymal characteristic [ 15 , 22 ].…”

Section: Discussionmentioning

confidence: 99%

Tumorigenic hybrids between mesenchymal stem cells and gastric cancer cells enhanced cancer proliferation, migration and stemness

et al. 2015

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BackgroundEmerging evidence indicates that inappropriate cell-cell fusion might contribute to cancer progression. Similarly, mesenchymal stem cells (MSCs) can also fuse with other cells spontaneously and capable of adopting the phenotype of other cells. The aim of our study was to investigate the role of MSCs participated cell fusion in the tumorigenesis of gastric cancer.MethodsWe fused human umbilical cord mesenchymal stem cells (hucMSCs) with gastric cancer cells in vitro by polyethylene glycol (PEG), the hybrid cells were sorted by flow cytometer. The growth and migration of hybrids were assessed by cell counting、cell colony formation and transwell assays. The proteins and genes related to epithelial- mesenchymal transition and stemness were tested by western blot、immunocytochemistry and real-time RT-PCR. The expression of CD44 and CD133 was examined by immunocytochemistry and flow cytometry. The xenograft assay was used to evaluation the tumorigenesis of the hybrids.ResultsThe obtained hybrids exhibited epithelial- mesenchymal transition (EMT) change with down-regulation of E-cadherin and up-regulation of Vimentin, N-cadherin, α-smooth muscle actin (α-SMA), and fibroblast activation protein (FAP). The hybrids also increased expression of stemness factors Oct4, Nanog, Sox2 and Lin28. The expression of CD44 and CD133 on hybrid cells was stronger than parental gastric cancer cells. Moreover, the migration and proliferation of heterotypic hybrids were enhanced. In addition, the heterotypic hybrids promoted the growth abilities of gastric xenograft tumor in vivo.ConclusionsTaken together, our results suggest that cell fusion between hucMSCs and gastric cancer cells could contribute to tumorigenic hybrids with EMT and stem cell-like properties, which may provide a flexible tool for investigating the roles of MSCs in gastric cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1780-1) contains supplementary material, which is available to authorized users.

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“…Stromal cells within a tumor can be truly malignant and have been reported as early as 1981 (28), although it remains under investigation (30)(31)(32)(33)(34)(49)(50)(51). Since it is almost impossible to distinguish between the tumor and stroma, in vitro studies involving direct or indirect co-culturing have been performed.…”

Section: Discussionmentioning

confidence: 99%

Malignant transformation of host stromal fibroblasts derived from the bone marrow traced in a dual-color fluorescence xenograft tumor model

Chen

et al. 2015

Oncology Reports

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Abstract. Solid tumors are abnormal tissues containing tumor and non-tumor cells, also known as tumor stromal cells. However, the malignant potential of tumor stromal cells remains largely unknown. The aim of the present study was to investigate the malignant potential of host bone marrow-derived stroma cells in transplanted subcutaneous tumors of the glioma stem/progenitor cells (GSPCs) labeled using the dual-color fluorescent tracer technique. The previously established human glioma stem/progenitor cell line SU3 was transfected with red fluorescence protein (SU3-RFP) and transplanted subcutaneously into green fluorescent protein (GFP) transgenic nude mice and chimeric mice in which GFP was only expressed by bone marrow-derived cells (BMDCs). The xenograft tumors were subcultured in vitro and two immortalized GFP-expressing stromal cell lines were cloned from the transplanted tumors. The two cloned cell lines showed an accelerated growth rate, loss of cell contact inhibition, high cloning efficiency, and high DNA content and telocentric (murine) chromosomes with heteroploid characteristics. The tumorigenesis rate (10/10, 1x10 6 ) of these host stromal cells was further evidence of malignant transformation. Immunofluorescence assay of the two host cell lines showed that they expressed fibroblast markers such as FAP, S100A4 and α-SMA, as well as mesenchymal cell markers such as CD44 and CD105. In conclusion, bone marrow-derived stromal fibroblasts recruited to tumors have the potential for malignant transformation induced by the tumor microenvironment, which provides new evidence for the role of the stroma in malignant transformation.

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

Cited by 40 publications

References 19 publications

Lipopolysaccharide (LPS) Promotes Apoptosis in Human Breast Epithelial × Breast Cancer Hybrids, but Not in Parental Cells

Lipopolysaccharide (LPS) Promotes Apoptosis in Human Breast Epithelial × Breast Cancer Hybrids, but Not in Parental Cells

Tumorigenic hybrids between mesenchymal stem cells and gastric cancer cells enhanced cancer proliferation, migration and stemness

Malignant transformation of host stromal fibroblasts derived from the bone marrow traced in a dual-color fluorescence xenograft tumor model

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