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Blood, 15 April 2007, Vol. 109, No. 8, pp. 3424-3431. Prepublished online as a Blood First Edition Paper on December 27, 2006; DOI 10.1182/blood-2006-09-048686. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2006-09-048686v1 109/8/3424    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Hirbe, A. C Articles by Weilbaecher, K. Search for Related Content PubMed PubMed Citation Articles by Hirbe, A. C Articles by Weilbaecher, K. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted September 25, 2006 Accepted December 9, 2006 Granulocyte colony-stimulating factor enhances bone tumor growth in mice in an osteoclast-dependent manner Angela C Hirbe, Ozge Uluckan, Elizabeth A Morgan, Mark C Eagleton, Julie L Prior, David Piwnica-Worms, Kathryn Trinkaus, Anthony Apicelli, and Katherine Weilbaecher* Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, MO, United States Molecular Imaging Center Mallinckrodt Institute of Radiology, Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, MO, United States Division of Biostatistics, Washington University School of Medicine, St. Louis, MO, United States * Corresponding author; email: kweilbae{at}im.wustl.edu. Inhibition of osteoclast activity has been associated with decreased tumor growth in bone in animal models. Increased recognition of factors that promote osteoclastic bone resorption in cancer patients led us to investigate whether increased osteoclast activation could enhance tumor growth in bone. Granulocyte colony-stimulating factor (G-CSF) is used to treat chemotherapy-induced neutropenia, but is also associated with increased markers of osteoclast (OC) activity and decreased bone mineral density (BMD). We used G-CSF as a tool to investigate the impact of increased OC activity on tumor growth in two murine osteolytic tumor models. An eight-day course of G-CSF alone (without chemotherapy) significantly decreased BMD and increased OC perimeter along bone in mice. Mice administered G-CSF alone demonstrated significantly increased tumor growth in bone as quantitated by in vivo bioluminescence imaging and histologic bone marrow tumor analysis. Short-term administration of AMD3100, a CXCR4 inhibitor, that mobilizes neutrophils with little effect on bone resorption, did not lead to increased tumor burden. However, osteoclast-defective osteoprotegerin transgenic (OPGTg) mice and bisphosphonate-treated mice were resistant to the effects of G-CSF administration upon bone tumor growth. These data demonstrate a G-CSF-induced stimulation of tumor growth in bone that is osteoclast dependent. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Filgrastim therapy: a bone of contention Elisabeth G. Blanchard and Seth J. Corey Blood 2007 109: 3125-3126. [Full Text] [PDF] This article has been cited by other articles: O. Uluckan, S. N. Becker, H. Deng, W. Zou, J. L. Prior, D. Piwnica-Worms, W. A. Frazier, and K. N. Weilbaecher CD47 Regulates Bone Mass and Tumor Metastasis to Bone Cancer Res., April 1, 2009; 69(7): 3196 - 3204. [Abstract] [Full Text] [PDF] K. Horiuchi, T. Kimura, T. Miyamoto, K. Miyamoto, H. Akiyama, H. Takaishi, H. Morioka, T. Nakamura, Y. Okada, C. P. Blobel, et al. Conditional Inactivation of TACE by a Sox9 Promoter Leads to Osteoporosis and Increased Granulopoiesis via Dysregulation of IL-17 and G-CSF J. Immunol., February 15, 2009; 182(4): 2093 - 2101. [Abstract] [Full Text] [PDF] Z. Xu, M. A. Hurchla, H. Deng, O. Uluckan, F. Bu, A. Berdy, M. C. Eagleton, E. A. Heller, D. H. Floyd, W. P. Dirksen, et al. Interferon-{gamma} Targets Cancer Cells and Osteoclasts to Prevent Tumor-associated Bone Loss and Bone Metastases J. Biol. Chem., February 13, 2009; 284(7): 4658 - 4666. [Abstract] [Full Text] [PDF] S. Vaira, T. Johnson, A. C. Hirbe, M. Alhawagri, I. Anwisye, B. Sammut, J. O'Neal, W. Zou, K. N. Weilbaecher, R. Faccio, et al. RelB is the NF-{kappa}B subunit downstream of NIK responsible for osteoclast differentiation PNAS, March 11, 2008; 105(10): 3897 - 3902. [Abstract] [Full Text] [PDF] A. C. Hirbe, J. Rubin, O. Uluckan, E. A. Morgan, M. C. Eagleton, J. L. Prior, D. Piwnica-Worms, and K. N. Weilbaecher Disruption of CXCR4 enhances osteoclastogenesis and tumor growth in bone PNAS, August 28, 2007; 104(35): 14062 - 14067. [Abstract] [Full Text] [PDF]

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