TY - JOUR
T1 - Mouse model recapitulates the phenotypic heterogeneity of human adult T-cell leukemia/lymphoma in bone
AU - Kohart, Nicole A.
AU - Elshafae, Said M.
AU - Supsahvad, Wachirapan
AU - Alasonyalilar-Demirer, Aylin
AU - Panfil, Amanda R.
AU - Xiang, Jingyu
AU - Dirksen, Wessel P.
AU - Veis, Deborah J.
AU - Green, Patrick L.
AU - Weilbaecher, Katherine N.
AU - Rosol, Thomas J.
N1 - Publisher Copyright:
© 2019 The Authors
PY - 2019/12
Y1 - 2019/12
N2 - 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.
AB - 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.
KW - Bone resorption
KW - HTLV-1
KW - Lymphoma
KW - Metastasis
KW - Mouse model
UR - http://www.scopus.com/inward/record.url?scp=85074028945&partnerID=8YFLogxK
U2 - 10.1016/j.jbo.2019.100257
DO - 10.1016/j.jbo.2019.100257
M3 - Article
C2 - 31871882
AN - SCOPUS:85074028945
SN - 2212-1374
VL - 19
JO - Journal of Bone Oncology
JF - Journal of Bone Oncology
M1 - 100257
ER -