Targeting sarcoma tumor-initiating cells through differentiation therapy
Human leukocyte antigen class I (HLA-I) down-regulation has been reported in many human cancers to be associated with poor clinical outcome. However, its connection to tumor-initiating cells (TICs) remains unknown. In this study, we report that HLA-I is down-regulated in a subpopulation of cells tha...
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| Format: | Article |
| Language: | English |
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Elsevier
2017-05-01
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| Series: | Stem Cell Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1873506117300703 |
| _version_ | 1818996011191762944 |
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| author | Dan Han Veronica Rodriguez-Bravo Elizabeth Charytonowicz Elizabeth Demicco Josep Domingo-Domenech Robert G. Maki Carlos Cordon-Cardo |
| author_facet | Dan Han Veronica Rodriguez-Bravo Elizabeth Charytonowicz Elizabeth Demicco Josep Domingo-Domenech Robert G. Maki Carlos Cordon-Cardo |
| author_sort | Dan Han |
| collection | DOAJ |
| description | Human leukocyte antigen class I (HLA-I) down-regulation has been reported in many human cancers to be associated with poor clinical outcome. However, its connection to tumor-initiating cells (TICs) remains unknown. In this study, we report that HLA-I is down-regulated in a subpopulation of cells that have high tumor initiating capacity in different types of human sarcomas. Detailed characterization revealed their distinct molecular profiles regarding proliferation, apoptosis and stemness programs. Notably, these TICs can be induced to differentiate along distinct mesenchymal lineages, including the osteogenic pathway. The retinoic acid receptor signaling pathway is overexpressed in HLA-1 negative TICs. All-trans retinoic acid treatment successfully induced osteogenic differentiation of this subpopulation, in vitro and in vivo, resulting in significantly decreased tumor formation. Thus, our findings indicate down-regulated HLA-I is a shared feature of TICs in a variety of human sarcomas, and differentiation therapy strategies may specifically target undifferentiated TICs and inhibit tumor formation. |
| first_indexed | 2024-12-20T21:22:57Z |
| format | Article |
| id | doaj.art-73d3562a4d3045128bb12f2d7db45bda |
| institution | Directory Open Access Journal |
| issn | 1873-5061 1876-7753 |
| language | English |
| last_indexed | 2024-12-20T21:22:57Z |
| publishDate | 2017-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Stem Cell Research |
| spelling | doaj.art-73d3562a4d3045128bb12f2d7db45bda2022-12-21T19:26:14ZengElsevierStem Cell Research1873-50611876-77532017-05-0121C11712310.1016/j.scr.2017.04.004Targeting sarcoma tumor-initiating cells through differentiation therapyDan Han0Veronica Rodriguez-Bravo1Elizabeth Charytonowicz2Elizabeth Demicco3Josep Domingo-Domenech4Robert G. Maki5Carlos Cordon-Cardo6Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USADepartment of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USADepartment of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USADepartment of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USADepartment of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USADepartment of Hematology-Oncology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USADepartment of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USAHuman leukocyte antigen class I (HLA-I) down-regulation has been reported in many human cancers to be associated with poor clinical outcome. However, its connection to tumor-initiating cells (TICs) remains unknown. In this study, we report that HLA-I is down-regulated in a subpopulation of cells that have high tumor initiating capacity in different types of human sarcomas. Detailed characterization revealed their distinct molecular profiles regarding proliferation, apoptosis and stemness programs. Notably, these TICs can be induced to differentiate along distinct mesenchymal lineages, including the osteogenic pathway. The retinoic acid receptor signaling pathway is overexpressed in HLA-1 negative TICs. All-trans retinoic acid treatment successfully induced osteogenic differentiation of this subpopulation, in vitro and in vivo, resulting in significantly decreased tumor formation. Thus, our findings indicate down-regulated HLA-I is a shared feature of TICs in a variety of human sarcomas, and differentiation therapy strategies may specifically target undifferentiated TICs and inhibit tumor formation.http://www.sciencedirect.com/science/article/pii/S1873506117300703Human leukocyte antigen class ITumor-initiating cellsSarcomas |
| spellingShingle | Dan Han Veronica Rodriguez-Bravo Elizabeth Charytonowicz Elizabeth Demicco Josep Domingo-Domenech Robert G. Maki Carlos Cordon-Cardo Targeting sarcoma tumor-initiating cells through differentiation therapy Stem Cell Research Human leukocyte antigen class I Tumor-initiating cells Sarcomas |
| title | Targeting sarcoma tumor-initiating cells through differentiation therapy |
| title_full | Targeting sarcoma tumor-initiating cells through differentiation therapy |
| title_fullStr | Targeting sarcoma tumor-initiating cells through differentiation therapy |
| title_full_unstemmed | Targeting sarcoma tumor-initiating cells through differentiation therapy |
| title_short | Targeting sarcoma tumor-initiating cells through differentiation therapy |
| title_sort | targeting sarcoma tumor initiating cells through differentiation therapy |
| topic | Human leukocyte antigen class I Tumor-initiating cells Sarcomas |
| url | http://www.sciencedirect.com/science/article/pii/S1873506117300703 |
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