Publication: Parathyroid hormone-related protein promotes bone loss in T-cell leukemia as well as in solid tumors
Date
2020-01-28
Authors
Authors
Kohart, Nicole A.
Elshafae, Said M.
Demirer, Aylin A.
Dirksen, Wessel P.
Breitbach, Justin T.
Shu, Sherry T.
Xiang, Jingyu
Weilbaecher, Katherine N.
Rosol, Thomas J.
Journal Title
Journal ISSN
Volume Title
Publisher
Taylor & Francis
Abstract
Parathyroid hormone-related protein (PTHrP) and macrophage inflammatory protein-1 alpha (MIP-1 alpha) are important factors that increase bone resorption and hypercalcemia in adult T-cell leukemia (ATL). We investigated the role of PTHrP and MIP-1 alpha in the development of local osteolytic lesions in T-cell leukemia through overexpression in Jurkat T-cells. Injections of Jurkat-PTHrP and Jurkat-MIP-1 alpha into the tibia and the left ventricle of NSG mice were performed to evaluate tumor growth and metastasis in vivo. Jurkat-pcDNA tibial neoplasms grew at a significantly greater rate and total tibial tumor burden was significantly greater than Jurkat-PTHrP neoplasms. Despite the lower tibial tumor burden, Jurkat-PTHrP bone neoplasms had significantly greater osteolysis than Jurkat-pcDNA and Jurkat-MIP-1 alpha neoplasms. Jurkat-PTHrP and Jurkat-pcDNA cells preferentially metastasized to bone following intracardiac injection, though the overall metastatic burden was lower in Jurkat-PTHrP mice. These findings demonstrate that PTHrP induced pathologic osteolysis in T-cell leukemia but did not increase the incidence of skeletal metastasis.
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Keywords
Macrophage-inflammatory protein-1-alpha, Serum-levels, Mouse model, Hypercalcemia, Expression, Pthrp, Metastases, Htlv-1, Leukemia/lymphoma, Localization, Cell lines and animal models, T-cell leukemia, Pthrp, Mip-1 alpha, Metastasis, Bone resorption, Oncology, Hematology
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