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Mouse model recapitulates the phenotypic heterogeneity of human adult T-cell leukemia/lymphoma in bone
- Source :
- Journal of Bone Oncology, Journal of Bone Oncology, Vol 19, Iss, Pp-(2019)
- Publication Year :
- 2019
- Publisher :
- Elsevier BV, 2019.
-
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
- 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
Subjects
Details
- ISSN :
- 22121374
- Volume :
- 19
- Database :
- OpenAIRE
- Journal :
- Journal of Bone Oncology
- Accession number :
- edsair.doi.dedup.....2dffdc06c9e78939eb20301f63a61de4