Transformation potential of bone marrow stromal cells into undifferentiated high-grade pleomorphic sarcoma |
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Authors: | Qing Li Hiroko Hisha Takashi Takaki Yasushi Adachi Ming Li Changye Song Wei Feng Satoshi Okazaki Tomomi Mizokami Junko Kato Muneo Inaba Naoki Hosaka Masahiko Maki Susumu Ikehara |
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Institution: | 1. First Department of Pathology, Kansai Medical University, Moriguchi City, Osaka, Japan 2. Department of Transplantation for Regeneration Therapy (Sponsored by Otsuka Pharmaceutical Co. Ltd.), Kansai Medical University, Moriguchi City, Osaka, Japan 3. Japan Cellnet, Ltd., Kyoto, Japan 4. First Department of Pathology, Transplantation Center, Center for Cancer Therapy, Regeneration Research Center for Intractable Diseases, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi City, Osaka, Japan
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Abstract: | Purpose Bone marrow adherent cells contain conventional bone marrow stromal cells and mesenchymal stem cells and these cells constitute the hematopoietic microenvironment. Mesenchymal stem cells have the capacity to give rise to multiple mesenchymal lineage cells and even ectodermal lineage cells. In the present study, we investigated what types of tumor cells are inducible from BM adherent cells by chemical carcinogens. Methods Bone marrow cells from neonatal C3H/HeN mice were collected within 24 h after birth and then cultured. Four days later, bone marrow adherent cells were obtained and the cells were treated with 3-methylcholanthrene. Results By this treatment, some transformed clones consisting of large spindle cells were obtained. The transformed cells were highly positive for CD44 and were positive for Sca-1, CD49d and CD106, whereas the cells were negative for hematolymphoid markers. The cell clones had the ability to support hematopoiesis in vitro. These results indicate that the transformed cell lines have the characteristics of BM stromal cells/mesenchymal stem cells. Moreover, during culture of the transformed cells, spontaneous bone nodule formation was observed. When the transformed cells were inoculated into immunodeficient mice subcutaneously, the neoplasms grew in the subcutaneous tissue of the mice. Microscopically and ultrastructurally, the neoplasms showed the typical morphology of undifferentiated high-grade pleomorphic sarcoma (UHGPS). Bone-related genes have been found to be expressed in both transformed cells and UHGPSs. Conclusion The present study suggests that UHGPSs are derived from BM stromal cells, probably mesenchymal stem cells. |
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