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Parathyroid hormone-related protein promotes bone loss in T-cell leukemia as well as in solid tumors

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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.

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Taylor & Francis

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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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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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