Histogenetic Characterization of Giant Cell Tumor of Bone

Salerno, Manuela; Avnet, Sofia; Alberghini, Marco; Giunti, Armando; Baldini, Nicola

doi:10.1007/s11999-008-0327-z

Cited by 60 publications

(50 citation statements)

References 40 publications

(64 reference statements)

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“…The expression of osteoclastogenic factors by giant cells may represent a positive feedback autocrine mechanism that promotes osteoclast recruitment and formation in GCTB. 28 Expression of osteoclastogenic factors by GCTB mononuclear cells is in keeping with the hypothesis that these cells express growth factors promoting osteoclast formation. 20,29 VEGF-A and RANKL expression by GCTB giant cells and M-CSF expression in enriched cultures of GCTB giant cells has been reported in previous studies.…”

Section: Osteoclastogenesis By M-csf Substitutes Rm Taylor Et Alsupporting

confidence: 64%

VEGF, FLT3 ligand, PlGF and HGF can substitute for M-CSF to induce human osteoclast formation: implications for giant cell tumour pathobiology

Taylor

Kashima

Knowles

et al. 2012

Laboratory Investigation

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Giant cell tumour of bone (GCTB) is a primary bone tumour that contains numerous very large, hyper-nucleated osteoclastic giant cells. Osteoclasts form from CD14 þ monocytes and macrophages in the presence of receptor activator of nuclear factor kappa B ligand (RANKL) and macrophage-colony stimulating factor (M-CSF). GCTB contains numerous growth factors, some of which have been reported to influence osteoclastogenesis and resorption. We investigated whether these growth factors are capable of substituting for M-CSF to support osteoclast formation from cultured human monocytes and whether they influence osteoclast cytomorphology and resorption. Vascular endothelial growth factor-A (VEGF-A), VEGF-D, FLT3 ligand (FL), placental growth factor (PlGF) and hepatocyte growth factor (HGF) supported RANKL-induced osteoclastogenesis in the absence of M-CSF, resulting in the formation of numerous TRAP þ multinucleated cells capable of lacunar resorption. Monocytes cultured in the presence of M-CSF, HGF, VEGF-A and RANKL together resulted in the formation of very large, hyper-nucleated (GCTB-like) osteoclasts that were hyper-resorptive. M-CSF and M-CSF substitute growth factors were identified immunohistochemically in GCTB tissue sections and these factors stimulated the resorption of osteoclasts derived from a subset of GCTBs. Our findings indicate that there are growth factors that are capable of substituting for M-CSF to induce human osteoclast formation and that these factors are present in GCTB where they influence osteoclast cytomorphology and have a role in osteoclast formation and resorption activity. The osteoclast is a multinucleated cell, which is formed from circulating mononuclear phagocyte precursors derived from the bone marrow. 1,2 It exhibits a number of specialised cytochemical and functional features, including the ability to carry out lacunar bone resorption. Increased osteoclast formation and activity is seen in a number of osteolytic bone and joint conditions, including notably giant cell tumour of bone (GCTB), a primary bone tumour, which contains numerous, very large, often hyper-nucleated osteoclastic giant cells that effect a considerable amount of bone resorption. 3,4 Osteoclast differentiation from monocyte or macrophage precursors requires the presence of receptor activator of nuclear factor kappa B ligand (RANKL) and macrophage-colony stimulating factor (M-CSF). 5 The importance of M-CSF in osteoclast formation is evidenced by the fact that in op/op osteopetrotic mice, which have a mutation in the M-CSF gene, very few osteoclasts are found in bone and there is markedly decreased bone resorption. 6,7 M-CSF promotes several aspects of osteoclastogenesis including the proliferation and fusion of osteoclast precursors as well as osteoclasts and the expression of the RANKL receptor by these cells. [8][9][10] The effect of M-CSF on mature osteoclast resorption activity is controversial with both a decrease and increase in lacunar resorption being reported. [11][12][13] Although bone resorption is gre...

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Section: Osteoclastogenesis By M-csf Substitutes Rm Taylor Et Alsupporting

confidence: 64%

VEGF, FLT3 ligand, PlGF and HGF can substitute for M-CSF to induce human osteoclast formation: implications for giant cell tumour pathobiology

Taylor

Kashima

Knowles

et al. 2012

Laboratory Investigation

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“…41,42 The pattern of staining with RUNX2 in only a few stromal cells of GCT supports that the neoplastic cells are likely only small component of a heterogeneous population. 23,41 Interestingly, predominantly low-grade osteosarcomas clustered together with giant cell tumors.…”

Section: Discussionmentioning

confidence: 76%

Regulators of skeletal development: a cluster analysis of 206 bone tumors reveals diagnostically useful markers

et al. 2012

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The molecules Indian hedgehog (IHH), SP7 (also known as osterix), sex-determining region Y-box 9 (SOX9), runt-related transcription factor 2 (RUNX2) and TWIST1 regulate the normal differentiation of osteo-and chondrogenic cells from precursors during skeletal development and remodeling. The aberrant function of the same molecules has been implicated in the pathogenesis of bone tumors. Preliminary studies suggest that antibodies against these molecules have practical, diagnostic or prognostic utility in tumors. However, a comprehensive analysis of the expression of these molecules in a large, diverse set of bone tumors has yet to be reported. The goals of this study were to compare the immunohistochemical profiles of IHH, SP7, SOX9, RUNX2 and TWIST1 among bone tumors and to determine the optimum panel for diagnostic utility. Tissue microarrays prepared from 206 undecalcified tumors (71 osteosarcomas, 26 osteoblastomas/osteoid osteomas, 50 giant cell tumors, 5 chondromyxoid fibromas and 54 chondroblastomas) were stained with antibodies to IHH, SP7, SOX9, RUNX2 and TWIST1. The stains were scored for intensity (0À3 þ ) and distribution. The results were analyzed by cluster analysis. Optimum antibody panels for diagnostic sensitivity and specificity were calculated. Analysis revealed six main clusters that corresponded well to tumor types and suggested a close relationship between the stromal cells of giant cell tumor and the osteoblasts of osteosarcoma. The expression profile of chondromyxoid fibroma and chondroblastoma also suggested related differentiation. The distribution of osteoblastomas and osteoid osteomas was more heterogeneous. RUNX2, SOX9 and TWIST1 represented the most sensitive and specific immunohistochemical panel to distinguish among these diagnoses with the limitation that no result could discriminate between chondroblastoma and chondromyxoid fibroma. IHH and SP7 did not yield additional utility.

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“…Although stromal cells from giant cell tumor expressed early osteogenic markers, they were unable to differentiate into osteoblasts, and did express intracellular adhesion molecule-I, which is a marker of bone-lining cells. They were unable to promote osteoclast differentiation,although they exerted a strong chemotactic effect on osteoclast precursors (47). Tenascin C (48) and other biomarkers (49) were identified as predictors of aggressive behaviour.…”

Section: Bone Tumoursmentioning

confidence: 99%

Orthopaedic Research in Italy: State of the Art

Cenni

Scioscia²,

Baldini

2011

Int J Immunopathol Pharmacol

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The most significant results in experimental and clinical orthopaedic research in Italy within the last three years have been primarily in major congenital diseases, bone tumors, regenerative medicine, joint replacements, spine, tendons and ligaments, The data presented in the following discussion is comparable with leading international results, highlighting Italian orthopaedic research excellemce as well as its shortcomings.There has been continued innovation in orthopaedic research over the past years. The advances in basic science, particularly in molecular and cell biology, in material science and in nanotechnology, has provided the tools for bone engineering, bone imaging and innovative methods for diagnosis and treatment of primitive and metastatic bone tumours. At this point, it seems necessary to examine to what extent are the limitations of these new orthopaedic techniques as well as the prevalent topics that should be explored and the position of the Italian orthopedic research on a global stage.

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Histogenetic Characterization of Giant Cell Tumor of Bone

Cited by 60 publications

References 40 publications

VEGF, FLT3 ligand, PlGF and HGF can substitute for M-CSF to induce human osteoclast formation: implications for giant cell tumour pathobiology

VEGF, FLT3 ligand, PlGF and HGF can substitute for M-CSF to induce human osteoclast formation: implications for giant cell tumour pathobiology

Regulators of skeletal development: a cluster analysis of 206 bone tumors reveals diagnostically useful markers

Orthopaedic Research in Italy: State of the Art

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