1. Mouse model recapitulates the phenotypic heterogeneity of human adult T-cell leukemia/lymphoma in bone
- Author
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Patrick L. Green, Amanda R. Panfil, Jingyu Xiang, Said M. Elshafae, Aylin Alasonyalilar-Demirer, Wachirapan Supsahvad, Deborah J. Veis, Nicole A. Kohart, Katherine N. Weilbaecher, Thomas J. Rosol, and Wessel P. Dirksen
- Subjects
ATL, adult T-cell leukemia/lymphoma ,0301 basic medicine ,lcsh:Diseases of the musculoskeletal system ,Osteolysis ,Lymphoma ,HHM, humoral hypercalcemia of malignancy ,Bone resorption ,lcsh:RC254-282 ,Jurkat cells ,Mouse model ,Metastasis ,NSG, NOD-scid IL2Rgammanull ,03 medical and health sciences ,0302 clinical medicine ,immune system diseases ,hemic and lymphatic diseases ,Bone cell ,medicine ,Tax, transcriptional activator from the X region ,business.industry ,HTLV-1, Human T-cell leukemia virus type 1 ,Hbz, HTLV-1 basic zipper protein ,μCT, micro-computed tomography ,SCID, CB17-Prkdcscid ,qRT-PCR, quantitative real-time polymerase chain reaction ,Bone metastasis ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,3. Good health ,Leukemia ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,HTLV-1 ,030220 oncology & carcinogenesis ,Cancer research ,Bone marrow ,lcsh:RC925-935 ,NOD, non-obese diabetic ,business ,NK, natural killer ,Research Article - Abstract
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. Keywords: HTLV-1, Lymphoma, Mouse model, Metastasis, Bone resorption
- Published
- 2019