Suppression of tumorigenesis by human mesenchymal stem cells in a hepatoma model.
Ling Qiao,Zhili Xu,Tiejun Zhao,Zhigang Zhao,Mingxia Shi,Robert Chunhua Zhao,Lihong Ye,Xiaodong Zhang +7 more
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It is demonstrated that hMSCs inhibit the malignant phenotypes of the H7402 and HepG2 human liver cancer cell lines, which include proliferation, colony-forming ability and oncogene expression both in vitro and in vivo.Abstract:
Human mesenchymal stem cells (hMSCs) can home to tumor sites and inhibit the growth of tumor cells. Little is known about the underlying molecular mechanisms that link hMSCs to the targeted inhibition of tumor cells. In this study, we investigated the effects of hMSCs on two human hepatoma cell lines (H7402 and HepG2) using an animal transplantation model, a co-culture system and conditioned media from hMSCs. Animal transplantation studies showed that the latent time for tumor formation was prolonged and that the tumor size was smaller when SCID mice were injected with H7402 cells and an equal number of Z3 hMSCs. When co-cultured with Z3 cells, H7402 cell proliferation decreased, apoptosis increased, and the expression of Bcl-2, c-Myc, proliferating cell nuclear antigen (PCNA) and survivin was downregulated. After treatment with conditioned media derived from Z3 hMSC cultures, H4702 cells showed decreased colony-forming ability and decreased proliferation. Immunoblot analysis showed that beta-catenin, Bcl-2, c-Myc, PCNA and survivin expression was downregulated in H7402 and HepG2 cells. Taken together, our findings demonstrate that hMSCs inhibit the malignant phenotypes of the H7402 and HepG2 human liver cancer cell lines, which include proliferation, colony-forming ability and oncogene expression both in vitro and in vivo. Furthermore, our studies provide evidence that the Wnt signaling pathway may have a role in hMSC-mediated targeting and tumor cell inhibition.read more
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Tannishtha Reya,Hans Clevers +1 more
TL;DR: Insights gained from understanding how the Wnt pathway is integrally involved in both stem cell and cancer cell maintenance and growth in the intestinal, epidermal and haematopoietic systems may serve as a paradigm for understanding the dual nature of self-renewal signals.
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Mesenchymal Stem Cells
TL;DR: The bone marrow contains multipotent MSC, which can be easily isolated and cultured in vitro, and the possibility of their clinical use in cell and gene therapy is analyzed.
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Stem Cells,Cancer and Cancer Stem Cells
TL;DR: Research data show that more resistant stem cells than common cancer cells exist in cancer patients, and to identify unrecognized differences between cancer stem cells and cancer cells might be able to develop effective classification, diagnose and treat for cancer.
Journal ArticleDOI
WNT and β-catenin signalling: diseases and therapies
TL;DR: WNT signalling has been studied primarily in developing embryos, but WNTs also have important functions in adults, and aberrant signalling by WNT pathways is linked to a range of diseases, most notably cancer.