Skeletal metastasis: Established and emerging roles of parathyroid hormone related protein (PTHrP) |
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Authors: | Jinhui Liao Laurie K McCauley |
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Institution: | (1) Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, MI 48109-1078, USA;(2) Department of Pathology, Medical School, University of Michigan, Ann Arbor, MI 48109-1078, USA |
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Abstract: | Parathyroid hormone related protein (PTHrP) is a well characterized tumor derived product that also has integral functions
in normal development and homeostasis. PTHrP is produced by virtually all tumor types that metastasize to bone and numerous
studies have demonstrated a correlation between PTHrP expression and skeletal localization of tumors. PTHrP has prominent
effects in bone via its interaction with the PTH-1 receptor on osteoblastic cells. Through indirect means, PTHrP supports
osteoclastogenesis by upregulating the receptor activator of NFκB ligand (RANKL) in osteoblasts. PTHrP also regulates osteoblast
proliferation and differentiation in manners that are temporal and dose dependent. Bone turnover has been implicated in the
localization of tumors to bone and PTHrP increases bone turnover. Bone turnover results in the release of growth factors such
as TGFβ and minerals such as calcium, both of which impact tumor cell growth and contribute to continued PTHrP production.
PTHrP also has anabolic properties and could be in part responsible for osteoblastic type reactions in prostate cancer. Finally,
emerging roles of PTH and PTHrP in the support of hematopoietic stem cell development in the bone marrow microenvironment
suggest that an interaction between hematopoietic cells and tumor cells warrants further investigation. |
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Keywords: | Parathyroid hormone related protein PTHrP Skeletal metastasis |
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