Mouse model recapitulates the phenotypic heterogeneity of human adult T-cell leukemia/lymphoma in bone.
Autor: | Kohart NA; Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA., Elshafae SM; Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA.; Department of Radiology, College of Medicine, The Ohio State University, Columbus, OH 43210, USA.; Department of Pathology, Faculty of Veterinary Medicine, Benha University, Kalyubia 3736, Egypt., Supsahvad W; Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA.; Department of Pathology, Faculty of Veterinary Medicine, Kasetsart University, Bangkok, Thailand., Alasonyalilar-Demirer A; Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA.; Department of Pathology, Faculty of Veterinary Medicine, Bursa Uludag University, 16059 Bursa, Turkey., Panfil AR; Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA., Xiang J; Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, MO 63110, USA., Dirksen WP; Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA., Veis DJ; Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, MO 63110, USA., Green PL; Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA., Weilbaecher KN; Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, MO 63110, USA., Rosol TJ; Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA.; Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, 225 Irvine Hall, Athens, OH 45701, USA. |
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Jazyk: | angličtina |
Zdroj: | Journal of bone oncology [J Bone Oncol] 2019 Aug 20; Vol. 19, pp. 100257. Date of Electronic Publication: 2019 Aug 20 (Print Publication: 2019). |
DOI: | 10.1016/j.jbo.2019.100257 |
Abstrakt: | Adult T-cell leukemia/lymphoma has a unique relationship to bone including latency in the marrow, and development of bone invasion, osteolytic tumors and humoral hypercalcemia of malignancy. To study these conditions, we established and characterized a novel mouse model of ATL bone metastasis. Patient-derived ATL cell lines including three that do not express HTLV-1 oncoprotein Tax (ATL-ED, RV-ATL, TL-Om1), an in vitro transformed human T-cell line with high Tax expression (HT-1RV), and an HTLV-1 negative T-cell lymphoma (Jurkat) were injected intratibially into NSG mice, and were capable of proliferating and modifying the bone microenvironment. Radiography, μCT, histopathology, immunohistochemistry, plasma calcium concentrations, and qRT-PCR for several tumor-bone signaling mRNAs were performed. Luciferase-positive ATL-ED bone tumors allowed for in vivo imaging and visualization of bone tumor growth and metastasis over time. ATL-ED and HT-1RV cells caused mixed osteolytic/osteoblastic bone tumors, TL-Om1 cells exhibited minimal bone involvement and aggressive local invasion into the adjacent soft tissues, Jurkat cells proliferated within bone marrow and induced minimal bone cell response, and RV-ATL cells caused marked osteolysis. This mouse model revealed important mechanisms of human ATL bone neoplasms and will be useful to investigate biological interactions, potential therapeutic targets, and new bone-targeted agents for the prevention of ATL metastases to bone. Competing Interests: None. (© 2019 The Authors.) |
Databáze: | MEDLINE |
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