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Xu Q.,Peking Union Medical College | Wang L.,Peking Union Medical College | Wang L.,Shengli Oilfield Center Hospital | Li H.,Peking Union Medical College | And 5 more authors.
International Journal of Oncology | Year: 2012

Although the epithelial-mesenchymal transition (EMT) is a normal process that occurs during development, it is thought to be associated with cancer progression and metastasis. Emerging evidence links mesenchymal stem cells (MSCs) in the tumor microenvironment with the occurrence of EMT in cancer progression. In this study, the human breast cancer cell line MCF7 was co-cultured with human adipose-derived MSCs (hAD-MSCs) in a transwell system. Co-cultured cells were analyzed for changes in cellular morphology, EMT markers, protein expression and tumor characteristics. We found that co-cultured MCF7 cells underwent EMT and established a stable mesenchymal phenotype after prolonged co-culturing. Here, we demonstrate that paracrine transforming growth factor-β1 (TGF-β1) secreted by hAD-MSCs regulated the establishment of EMT in MCF7 cells by targeting the ZEB/miR-200 regulatory loop. The downregulation of paracrine TGF-β1 levels can inhibit and reverse the EMT progress by downregulating ZEB1/2 and upregulating miR-200b and miR-200c. The maintenance of a stable mesenchymal state by MCF7 cells required the establishment of autocrine TGF-β signaling to drive and sustain ZEB expression, which had been initiated by the prolonged co-culturing with hAD-MSCs. These results suggest that MSCs may promote breast cancer metastasis by stimulating and facilitating the EMT process. Source

Wang L.,Shengli Oilfield Center Hospital | Xu M.,Shengli Oilfield Center Hospital | Zhang M.-H.,Shengli Oilfield Center Hospital | Xing J.,Shengli Oilfield Center Hospital | And 3 more authors.
Chinese Journal of Tissue Engineering Research | Year: 2014

Background: Clinical infusion of hematopoietic stem cells and mesenchymal stem cells for treatment of aplastic anemia has been reported. Objective: To investigate the effect of human adipose-derived mesenchymal stems cells on the secretion function of T lymphocytes of aplastic anemia patients. Methods: Human adipose-derived mesenchymal stems cells were extracted from healthy human adipose tissues. T-lymphocytes were harvested from peripheral blood of patients with aplastic anemia by density gradient centrifugation. Human adipose-derived mesenchymal stems cells were co-cultured with T-lymphocytes. The levels of interleukin-2, interleukin-4, interleukin-10 and interferon-γ were detected by enzyme linked immunosorbent assay. T-bet and GATA-3 levels were examined by real-time PCR and western blot. Results and Conclusion: The levels of Th1 type cytokines interferon-γ and interleukin-2 in the co-culture group were significantly lower than those in the T-lymphocyte group (P < 0.05). But the levels of Th2 type cytokines interleukin-4 and interleukin-10 in the co-culture group were significantly higher than those in the T-lymphocyte group (P < 0.05). The T-bet mRNA and protein levels in the co-culture group were significantly lower than those in the T-lymphocyte group, while the GATA-3 mRNA and protein levels were significantly higher in the co-culture group. Human adipose-derived mesenchymal stems cells can mediate an immunoregulation effect on T-lymphocytes of aplastic anemia patients in vitro, which is possibly related with the inhibition of Th1-dominant response due to the disorder of T-bet and GATA-3 gene expression. Source

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