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Expression of CXCR4 and CXCL12 (SDF-1) in human prostate cancers (PCa) in vivo

Authors

  • Yan-Xi Sun,

    1. Department of Periodontics, Prevention, Geriatrics, University of Michigan School of Dentistry, 1011 North University Ave., Ann Arbor, Michigan
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  • Jingcheng Wang,

    1. Department of Periodontics, Prevention, Geriatrics, University of Michigan School of Dentistry, 1011 North University Ave., Ann Arbor, Michigan
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  • Charles E. Shelburne,

    1. Department of Biologic and Materials Sciences, University of Michigan School of Dentistry, 1011 North University Ave., Ann Arbor, Michigan
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  • Dennis E. Lopatin,

    1. Department of Biologic and Materials Sciences, University of Michigan School of Dentistry, 1011 North University Ave., Ann Arbor, Michigan
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  • Arul M. Chinnaiyan,

    1. Department of Pathology and Urology, University of Michigan School of Medicine, 1301 Catherine Road, Ann Arbor, Michigan
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  • Mark A. Rubin,

    1. Department of Pathology, Brigham and Women's Hospital, 75 Francis Street, Boston, Massachusetts
    Current affiliation:
    1. Department of Pathology, Brigham and Women's Hospital, 75 Francis Street Boston, MA.
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  • Kenneth J. Pienta,

    1. Division of Hematology and Medical Oncology, Department of Internal Medicine, University of Michigan School of Medicine, 1500 E. Medical Center Drive, Ann Arbor, Michigan
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  • Russell S. Taichman

    Corresponding author
    1. Department of Periodontics, Prevention, Geriatrics, University of Michigan School of Dentistry, 1011 North University Ave., Ann Arbor, Michigan
    • Department of Periodontics, Prevention, Geriatrics, University of Michigan School of Dentistry, 1011 North University Ave., Ann Arbor, Michigan 48109-1078.
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Abstract

Human prostate cancers (PCa) express great variability in their ability to metastasize to bone. The identification of molecules associated with aggressive phenotypes will help to define PCa subsets and will ultimately lead to better treatment strategies. The chemokine stromal-derived factor-1 (SDF-1 or CXCL12) and its receptor CXCR4 are now known to modulate the migration and survival of an increasing array of normal and malignant cell types including breast, pancreatic cancers, glioblastomas, and others. The present investigation extends our previous investigations by determining the expression of CXCR4 and CXCL12 in humans using high-density tissue microarrays constructed from clinical samples obtained from a cohort of over 600 patients. These data demonstrate that CXCR4 protein expression is significantly elevated in localized and metastastic cancers. At the RNA level, human PCa tumors also express CXCR4 and message, but overall, they were not significantly different suggesting post-transcriptional regulation of the receptor plays a major role in regulating protein expression. Similar observations were made for CXCL12 message, but in this case more CXCL12 message was expressed by metastastic lesions as compared to normal tissues. PCa cell lines also express CXCL12 mRNA, and regulate mRNA expression in response to CXCL12 and secrete biologically active protein. Furthermore, neutralizing antibody to CXCL12 decreased the proliferation of bone homing LNCaP C4-2B and PC3 metastastic tumor cells. These investigations provide important new information pertaining to the molecular basis of how tumors may ‘home’ to bone, and the mechanisms that may account for their growth in selected end organs. © 2003 Wiley-Liss, Inc.

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