Mouse model recapitulates the phenotypic heterogeneity of human adult T-cell leukemia/lymphoma in bone.
J Bone Oncol
; 19: 100257, 2019 Dec.
Article
em En
| MEDLINE
| ID: mdl-31871882
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.
ATL, adult T-cell leukemia/lymphoma; Bone resorption; HHM, humoral hypercalcemia of malignancy; HTLV-1; HTLV-1, Human T-cell leukemia virus type 1; Hbz, HTLV-1 basic zipper protein; Lymphoma; Metastasis; Mouse model; NK, natural killer; NOD, non-obese diabetic; NSG, NOD-scid IL2Rgammanull; SCID, CB17-Prkdcscid; Tax, transcriptional activator from the X region; qRT-PCR, quantitative real-time polymerase chain reaction; µCT, micro-computed tomography
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MEDLINE
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En
Ano de publicação:
2019
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Article