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PTHrP and Skeletal Metatasis

  • Laurie K. McCauley
  • Abraham Schneider
Part of the Cancer Treatment and Research book series (CTAR, volume 118)

Abstract

Skeletal metastasis is a common event in many advanced-stage cancer patients, with half of the common primary tumors eventually metastasizing to bone (Rubens, 2000). In most cases, it is the metastasis rather than the primary tumor that is responsible for the cancer-associated mortality (Chambers et al., 2002). Certain solid tumors such as cancer of the prostate, breast, and lung preferentially metastasize to bone (Rubens, 2000; Mundy, 2002). All of these tumors have been found to produce parathyroid hormone-related protein (PTHrP) (Keller et al., 2001; Martin and Moseley, 2000; Käkönen and Mundy, 2003). The levels of PTHrP produced by tumors in the bone marrow are dramatically higher than what is normally produced by cells resident in bone and bone marrow thus setting up a scenario where the bone is exposed to supraphysiologic levels of this highly bone active cytokine. The precise levels of PTHrP in the bone marrow microenvironment in metastatic lesions and among various tumors are as yet unknown. Most studies have focused on circulating levels of PTHrP that are readily measurable but do not necessarily reflect the levels in the metastatic environment, and on the production of PTHrP by various tumor cell lines in vitro that may be very different than what the tumor produced in situ. Once in the bone marrow microenvironment, PTHrP is localized to its key target tissue, which is bone. For most tumors, PTHrP may be the most ‘boneactive’ cytokine produced in this lesion and hence understanding the actions of PTHrP are critical to the pathophysiology of bony metastases.

Keywords

Bone Metastasis Skeletal Metastasis Bone Marrow Microenvironment Bone Microenvironment Osteolytic Bone Metastasis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 2004

Authors and Affiliations

  • Laurie K. McCauley
    • 1
    • 2
  • Abraham Schneider
    • 1
  1. 1.Department of Periodontics/Prevention/Teriatrics, School of DentistryUniversity of MichiganUSA
  2. 2.Department of Pathology, Medical SchoolUniversity of MichiganUSA

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