An immunohistological study of giant‐cell tumour of bone: Evidence for an osteoclast origin of the giant cells

Athanasou, N A; Bliss, Eleanor A.; Gatter, K C; Heryet, A; Woods, C. G.; McGee, J O

doi:10.1002/path.1711470302

Cited by 62 publications

(23 citation statements)

References 13 publications

(6 reference statements)

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“…As a result of the presence of a remarkably high number of osteoclast-like GC, early researchers suggested GCT was a neoplasm of the osteoclastic lineage, hence the term ''osteoclastoma'' [7]. However, GC show typical features of normal osteoclasts, including calcitonin and vitronectin receptor expression, tartrate-resistant acid phosphatase (TRACP) activity, and lacunar resorption ability [1,14,30,35]. SC were therefore believed the most likely candidate neoplastic elements of GCT, partly based on their ability to grow both in vitro and in vivo [2,24].…”

Section: Introductionmentioning

confidence: 99%

Histogenetic Characterization of Giant Cell Tumor of Bone

Salerno

Avnet

Alberghini

et al. 2008

Clin Orthop Relat Res

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The unpredictable behavior of giant cell tumor (GCT) parallels its controversial histogenesis. Multinucleated giant cells, stromal cells, and CD68 + monocytes/ macrophages are the three elements that interact in GCT. We compared the ability of stromal cells and normal mesenchymal stromal cells to differentiate into osteoblasts. Stromal cells and mesenchymal cells had similar proliferation rates and lifespans. Although stromal cells expressed early osteogenic markers, they were unable to differentiate into osteoblasts but they did express intracellular adhesion molecule-1, a marker of bone-lining cells. They were unable to form clones in a semisolid medium and unable to promote osteoclast differentiation, although they exerted a strong chemotactic effect on osteoclast precursors. Stromal cells may be either immature proliferating osteogenic elements or specialized osteoblast-like cells that fail to show neoplastic features but can induce the differentiation of osteoclast precursors. They might be secondarily induced to proliferate by a paracrine effect induced by monocytemacrophages and/or giant cells. The increased number of giant cells in GCT may be secondary to an autocrine circuit mediated by the receptor activator of nuclear factor kB.

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Section: Introductionmentioning

confidence: 99%

Histogenetic Characterization of Giant Cell Tumor of Bone

Salerno

Avnet

Alberghini

et al. 2008

Clin Orthop Relat Res

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“…GCT are primary neoplasms of the skeleton [16] and cause extensive and destructive osteolysis [ll]. The histological makeup of giant cell tumors consists of three cell types: 1) mononuclear mesenchymal stromal cells, which represent the tumor (proliferating) component of GCT, 2 ) hematopoietic mononuclear osteoclast precursors, which resemble monocytes, and 3) multinucleated giant cells, which resemble osteoclasts [ 3,10,14].…”

Section: Introductionmentioning

confidence: 99%

Recruitment of osteoclast precursors by stromal cell derived factor‐1 (SDF‐1) in giant cell tumor of bone

Liao

Yurgelun

et al. 2005

Journal Orthopaedic Research

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Giant cell tumor (GCT) of bone is a unique bone lesion that is characterized by an excessive number of multinucleated osteoclasts. GCT consists of neoplastic stromal cells, multinucleated osteoclasts and their precursors, thus serving as a naturally occurring human disease model for the study of osteoclastogenesis. It still remains unclear how stromal cells of GCT recruit osteoclast precursors. In the present study, we characterized the cellular components of GCT and confirmed the presence of C D 14+-monocytes/CD68'-macrophages and CD34+-heniatopoetic stem cells that express CXCR4, a specific receptor for SDF-1; SDF-1 gene expression and presence of SDF-1 protein were confirmed by real time RT-PCR, in situ hybridization, and immunohistochemistry in the GCT tissue and cultured cells. SDF-1 was present at 25-50ng/ml in the conditioned media from the GCT cultures, which is in the range of physiological chemotactic concentration. Migration of osteoclast precursors was 2.5-fold higher in response to GCT conditioned media compared to the control media; and migration was inhibited by an average of 36% with anti-SDF-1 neutralizing antibody or competing recombinant SDF-1. These results suggest that SDF-1 is one of the significant chemoattractant factors involved in the recruitment of hematopoietic osteoclast precursor cells during tumor-induced osteoclastogenesis.

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“…GCT is one of a few neoplasms in which the macrophage/osteoclast precursor cells and osteoclast-like giant cells infiltrate the tumor mass. The majority of these infiltrating cells are CD68 ϩ and belong to the macrophage/osteoclast lineage [Burmester et al, 1983;Athanasou et al, 1985]. Our previous studies showed that the tumor cells of GCT are capable of producing transforming growth factor-␤1 (TGF-␤1), which stimulates recruitment of reactive osteoclasts [Zheng et al, 1994].…”

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confidence: 99%

Gene expression of monocyte chemoattractant protein-1 in giant cell tumors of bone osteoclastoma: Possible involvement in CD68+ macrophage-like cell migration

et al. 1998

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Giant cell tumor of bone (GCT) is one of a few neoplasms in which the macrophage/osteoclast precursor cells and osteoclast-like giant cells infiltrate the tumor mass. Monocyte chemoattractant protein 1 (MCP-1) is a potent chemotactic factor specific for monocytes. In search of relevant cytokines that may enhance the recruitment of these reactive cells, we evaluated the localization and regulation of MCP-1 mRNA and protein in GCT by using Northern blot analysis, in situ hybridization and immunohistochemistry. We also determined whether conditioned medium obtained from GCT cultures can recruit human peripheral blood monocytes (CD68+) in an in vitro chemotactic assay. Using Northern blot analysis, we detected the specific gene transcript for MCP-1 in all GCT samples tested. In situ hybridization and immunohistochemistry revealed that both MCP-1 gene transcript and protein were consistently present in the cytoplasm of stromal-like tumor cells of GCT. Treatment of mononuclear cells from GCT at third passage with TGF-beta1 for 24 h increased the level of MCP-1 mRNA in a dose-dependent manner, with the maximum effect at 1 ng/ml. Conditioned media from GCT cultures promoted the chemotactic migration of CD68+ peripheral monocytes, an activity which was abolished by the addition of MCP-1 antibody to the conditioned medium. Thus, the results of this study suggest that recruitment of CD68+ macrophage-like cells may be due to the production MCP-1 by stromal-like tumor cells. These CD68+ cells may originate from peripheral blood and could have the capability of further differentiating into osteoclasts in the tumor.

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An immunohistological study of giant‐cell tumour of bone: Evidence for an osteoclast origin of the giant cells

Cited by 62 publications

References 13 publications

Histogenetic Characterization of Giant Cell Tumor of Bone

Histogenetic Characterization of Giant Cell Tumor of Bone

Recruitment of osteoclast precursors by stromal cell derived factor‐1 (SDF‐1) in giant cell tumor of bone

Gene expression of monocyte chemoattractant protein-1 in giant cell tumors of bone osteoclastoma: Possible involvement in CD68+ macrophage-like cell migration

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