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Osteoprotegrin and the bone homing and colonization potential of breast cancer cells

Authors

  • Preeti Kapoor,

    1. Division of Musculoskeletal Sciences, Department of Orthopedics and Rehabilitation, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania
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  • Larry J. Suva,

    1. Department of Orthopedic Surgery, Center for Orthopaedic Research, University of Arkansas for Medical Sciences and Cancer Laboratory, Little Rock, Arkansas
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  • Danny R. Welch,

    1. Department of Pathology, University of Alabama, Birmingham, Alabama
    2. Comprehensive Cancer Center, University of Alabama, Birmingham, Alabama
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  • Henry J. Donahue

    Corresponding author
    1. Division of Musculoskeletal Sciences, Department of Orthopedics and Rehabilitation, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania
    2. Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania
    • Division of Musculoskeletal Sciences, Department of Orthopaedics and Rehabilitation, MC: H089, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033.
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Abstract

Breast cancer cells preferentially metastasize to bone, leading to the formation of primarily osteolytic lesions. Osteoprotegerin (OPG) plays multifactorial roles in the development of osteolytic bone metastases. An increase in the ratio of receptor activator of nuclear factor κB ligand (RANKL) to OPG increases osteoclastogenesis within the bone microenvironment. OPG also acts as a survival factor for cancer cells by protecting them from tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) mediated apoptosis. This study compares OPG production in vitro in a number of breast cancer cell lines exhibiting both differences in metastatic capacity and in preferential metastasis to bone. Our studies demonstrated that OPG expression by MDA-231, MDA-MET, and MDA-231/K cancer cells was directly correlated with bone specific homing and colonization potential but not with metastasis of cancer cells to other organs; both in IL-1β stimulated and control cells. We also demonstrated expression of other bone-related markers including type I collagen, osteocalcin, osteopontin, and Runx2 in these cells. However, the generally lower expression of these markers in the bone selective cell line MDA-MET suggested that increased OPG expression in the bone specific variant was not merely a consequence of enhanced osteomimicry by these cells but that it has a significant role in the metastatic process. Co-culture of breast cancer cells with osteoblastic cells (hFOB 1.19) led to an overall downregulation in OPG production, which was not affected by the bone homing and colonization potential of the cell lines, suggesting that OPG alone is not indicative of osteolytic bone activity by breast cancer cells. J. Cell. Biochem. 103: 30–41, 2008. © 2007 Wiley-Liss, Inc.

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