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Leuk Lymphoma. 2019 Oct 8:1-11. doi: 10.1080/10428194.2019.1672055. [Epub ahead of print]

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

Author information

1
Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University , Columbus , OH , USA.
2
Department of Pathology, Faculty of Veterinary Medicine, Benha University , Kalyubia , Egypt.
3
Department of Pathology, Faculty of Veterinary Medicine, Bursa Uludag University , Bursa , Turkey.
4
Department of Microbiology and Molecular Genetics, School of Medicine, University of Pittsburgh , Pittsburgh , PA , USA.
5
Department of Medicine, Division of Oncology, Washington University School of Medicine , St. Louis , MO , USA.
6
Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University , Athens , OH , USA.

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.

KEYWORDS:

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

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