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

Nicole A. Kohart, Said M. Elshafae, Aylin A. Demirer, Wessel P. Dirksen, Justin T. Breitbach, Sherry T. Shu, Jingyu Xiang, Katherine N. Weilbaecher, Thomas J. Rosol

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Parathyroid hormone-related protein (PTHrP) and macrophage inflammatory protein-1α (MIP-1α) are important factors that increase bone resorption and hypercalcemia in adult T-cell leukemia (ATL). We investigated the role of PTHrP and MIP-1α in the development of local osteolytic lesions in T-cell leukemia through overexpression in Jurkat T-cells. Injections of Jurkat-PTHrP and Jurkat-MIP-1α 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-1α 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.

Original languageEnglish
Pages (from-to)409-419
Number of pages11
JournalLeukemia and Lymphoma
Volume61
Issue number2
DOIs
StatePublished - Jan 28 2020

Keywords

  • Cell lines and animal models
  • MIP-1α
  • PTHrP
  • T-cell leukemia
  • bone resorption
  • metastasis

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