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Type: Journal article
Title: Molecular profiling of giant cell tumor of bone and the osteoclastic localization of ligand for receptor activator of nuclear factor kB
Author: Morgan, T.
Atkins, G.
Trivett, M.
Johnson, S.
Kansara, M.
Schlicht, S.
Slavin, J.
Simmons, P.
Dickinson, I.
Powell, G.
Choong, P.
Holloway, A.
Thomas, D.
Citation: American Journal of Pathology, 2005; 167(1):117-128
Publisher: Amer Soc Investigative Pathology Inc
Issue Date: 2005
ISSN: 0002-9440
Statement of
Teresa Morgan, Gerald J. Atkins, Melanie K. Trivett, Sandra A. Johnson, Maya Kansara, Stephen L. Schlicht, John L. Slavin, Paul Simmons, Ian Dickinson, Gerald Powell, Peter F.M. Choong, Andrew J. Holloway, and David M. Thomas
Abstract: Giant cell tumor of bone (GCT) is a generally benign, osteolytic neoplasm comprising stromal cells and osteoclast-like giant cells. The osteoclastic cells, which cause bony destruction, are thought to be recruited from normal monocytic pre-osteoclasts by stromal cell expression of the ligand for receptor activator of nuclear factor kappaB (RANKL). This model forms the foundation for clinical trials in GCTs of novel cancer therapeutics targeting RANKL. Using expression profiling, we identified both osteoblast and osteoclast signatures within GCTs, including key regulators of osteoclast differentiation and function such as RANKL, a C-type lectin, osteoprotegerin, and the wnt inhibitor SFRP4. After ex vivo generation of stromal- and osteoclast-enriched cultures, we unexpectedly found that RANKL mRNA and protein were more highly expressed in osteoclasts than in stromal cells, as determined by expression profiling, flow cytometry, immunohistochemistry, and reverse transcriptase-polymerase chain reaction. The expression patterns of molecules implicated in signaling between stromal cells and monocytic osteoclast precursors were analyzed in both primary and fractionated GCTs. Finally, using array-based comparative genomic hybridization, neither GCTs nor the derived stromal cells demonstrated significant genomic gains or losses. These data raise questions regarding the role of RANKL in GCTs that may be relevant to the development of molecularly targeted therapeutics for this disease.
Keywords: Osteoclasts; Humans; Liposarcoma; Giant Cell Tumor of Bone; Sarcoma, Synovial; Leiomyosarcoma; Bone Neoplasms; Proteins; Carrier Proteins; Membrane Glycoproteins; RNA, Messenger; DNA Primers; Flow Cytometry; Immunohistochemistry; Gene Expression Profiling; Reverse Transcriptase Polymerase Chain Reaction; Nucleic Acid Hybridization; Cell Differentiation; Gene Expression; Cell Lineage; Histiocytoma, Benign Fibrous; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B
Rights: © 2005 American Society for Investigative Pathology
RMID: 0020050661
DOI: 10.1016/S0002-9440(10)62959-8
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Appears in Collections:Orthopaedics and Trauma publications

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