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The role of the oncogenic TBX3 in the transformation of mesenchymal stem cells into a subset of sarcomas


                      Authors: Damerell, V. , Willmer, T. , du Toit, M. , Swartz, S. , Lennard, K. , Mulder, N. , Govender D. , Pepper, MS. and Prince, S. 1
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                      1 Department of Human Biology, Department of Integrative Biomedical Sciences, Department of Pathology, Faculty of Health Sciences, University of Cape Town, South Africa, Department of Immunology, Faculty of Health
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                      Sciences, University of Pretoria, South Africa, Biomedical Research and Innovation Platform, SAMRC, Tygerberg 7505, South Africa
           Empty #1            Empty #2                                                                                                                                  Synovial     Adjacent
                                                                                1                                             Liposarcoma Chondrosarcoma  Fibrosarcoma   sarcoma    normal tissue
                                                                                   TBX3 is upregulated
                                                                                    in sarcoma tissues                TBX3
                                                                                                                                                     Immunohistochemistry
           TBX3 #1             TBX3 #2                                                                                                    TBX3 FC relative to normal by stage  Logrank Test P-Value: 0.0591
                                                                                                                                            Fold change
                                                                                                                                   TBX3            p=0.02        TBX3





            3D-Spheroid invasion: 48 hours                                                                                                        I-III              IV
                                                                                                                                                  Tumour stage
                                            4                                                                           2                         PCR Array                Kaplan-Meier curve
                                              TBX3 promotes                                                               TBX3 promotes
                                               MSC invasion                                                              MSC proliferation
   MMP2                    70 kDa
          1.2   1.0  1.8   1.2   1.3
   MMP9                    70 kDa
          1.1  1.0   1.3   1.5   1.1
   β-actin                 43 kDa

    Western Blot: Invasion markers                                                                                                   TBX3                95 kDa
                                                                                                                                  Cyclin A               54 kDa      MTT Assay: Growth curve

                                                                                  3                                              Cyclin B1               54 kDa
                                                                                       TBX3 promotes                                CDK2                 34 kDa
                                                                                       MSC migration                               β-actin               43 kDa

                                             Migration Assay                                                                        Western Blot: Cell cycle markers
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