Cytological properties of stromal cells derived from giant cell tumor of bone (GCTSC) which can induce osteoclast formation of human blood monocytes without cell to cell contact

Nishimura, Makoto; Yuasa, Kimitaka; Mori, Kouki; Miyamoto, Naokazu; Ito, Morihiro; Tsurudome, Masato; Nishio, Machiko; Kawano, Mitsuo; Komada, Hiroshi; Uchida, Atsushi; Ito, Yasuhiko

doi:10.1016/j.orthres.2005.01.004

Cited by 46 publications

(42 citation statements)

References 31 publications

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“…This supposition is supported by the gene expression of additional markers of an early osteoblastic differentiation (e.g. collagen I, bone sialoprotein, and osteonectin) and the ability to differentiate osteoblasts (Cbfa-1, osterix, osteocalcin) under cell culture conditions [16,33,36]. A hypothesis is based on this fact that the neoplastic cells of the giant cell tumour (GCTSC) are derived histogenetically from osteoblastic cells.…”

Section: Differentiation Level Of the Neoplastic Stromal Cellsmentioning

confidence: 96%

“…In contrast, RANKL is expressed by the neoplastic GCTSC promoting the fusion of MNHC to MNGC, with macrophage colony-stimulating factor (M-CSF) acting as a co-factor [1,2,15]. Cell culture experiments have revealed that giant cell formation takes place even in the absence of any direct cell contact between GCTSC and MNHC [36]. In contrast, all three cell types of the GCT express the antagonistic ligand OPG [15].…”

Section: Functional Connections Between the Neoplastic And Non-neoplamentioning

confidence: 99%

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Giant cell tumour of bone: morphological, biological and histogenetical aspects

Werner

2006

International Orthopaedics (SICOT)

212

156

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The giant cell tumour of bone (GCT) is a locally aggressive intraosseous neoplasm of obscure biological behaviour. Although well defined in clinical, radiological and histological terms, detailed information on its biological development is still relatively incomplete. The tumoral tissue consists of three cell types -the neoplastic giant cell tumour stromal cells (GCTSC), representing the proliferative fraction, secondarily recruited mononuclear histiocytic cells (MNHC) and multinuclear giant cells (MNGC). These cellular components interact together with factors that have a role in regulating osteoclast function in normal bone tissue (e.g. RANK, RANKL, OPG, M-CSF). Recent publications suggest that the neoplastic stromal cells express differentiation features of mesenchymal stem cells. Further research of the pathogenesis of GCT as well as the complex interactions of its cellular populations may provide the knowledge necessary for developing approaches for a biological-based therapy of this neoplasm.Résumé Les tumeurs à cellules géantes (GCT) sont des tumeurs localement agressives de type néoplasme intra osseux don't les mécanismes biologiques restent relativement obscurs. Cependant si ces tumeurs sont bien définies sur le plan clinique, radiologique et histologique, les détails marquants de leur développement biologique restent inconnus. Le tissu tumoral consiste en un stroma de tumeurs à cellules géantes (GCTSC) qui représente la partie prolifér-ative de la tumeur avec adjonction secondaire de cellules de type histogitaire mononuclées (MNHC) et de cellules géantes (MNGC). Ces composants cellulaires interagissent avec un certain nombre de facteurs régulant l'action ostéoclastique du tissu osseux normal (e.g. RANK, RANKL, OPG, M-CSF). De récentes publications permettent de penser que ce stroma cellulaire de type néoplasique exprime une différenciation de cellules mésenchymateuses. De prochaines recherches sur la pathogénèse des tumeurs à cellules géantes ainsi que sur les interactions complexes des différentes populations cellulaires devraient permettre d'approcher un traitement médical pour ce type de néoplasme.

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Section: Differentiation Level Of the Neoplastic Stromal Cellsmentioning

confidence: 96%

Section: Functional Connections Between the Neoplastic And Non-neoplamentioning

confidence: 99%

Giant cell tumour of bone: morphological, biological and histogenetical aspects

Werner

2006

International Orthopaedics (SICOT)

212

156

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“…Histologically, GCTB is composed of sheets of neoplastic ovoid mononuclear cells with high RANK ligand (RANKL) expression, RANK-positive mononuclear cells of myeloid linage, and a randomly distributed population of large RANKexpressing osteoclast-like giant cells (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13). Many researchers have shown that the giant cell of GCTB is osteoclastic in nature (4,6,10) and that the true neoplastic cells are ovoid cells displaying markers of mesenchymal stem cells that have partially differentiated along the osteoblast lineage (14)(15)(16)(17). These tumors are frequently described to contain small areas of osteoid matrix deposition, woven bone, and occasionally new bone, which may be reactive tissue at the tumor margin or formed de novo within the tumor (9,18,19).…”

Section: Introductionmentioning

confidence: 99%

Denosumab Induces Tumor Reduction and Bone Formation in Patients with Giant-Cell Tumor of Bone

Branstetter

Nelson

Manivel

et al. 2012

Clinical Cancer Research

374

301

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Purpose: Giant-cell tumor of bone (GCTB) is a locally aggressive, benign osteolytic tumor in which bone destruction is mediated by RANK ligand (RANKL). The RANKL inhibitor denosumab is being investigated for treatment of GCTB. We describe histologic analyses of GCTB tumor samples from a phase II study of denosumab in GCTB.Experimental Design: Adult patients with recurrent or unresectable GCTB received subcutaneous denosumab 120 mg every 4 weeks (with additional doses on days 8 and 15). The primary histologic efficacy endpoint was the proportion of patients who had a 90% or more elimination of giant cells from their tumor. Baseline and on-study specimens were also evaluated for overall tumor morphology and expression of RANK and RANKL.Results: Baseline tumor samples were typically composed of densely cellular proliferative RANKLpositive tumor stromal cells, RANK-positive rounded mononuclear cells, abundant RANK-positive tumor giant cells, and areas of scant de novo osteoid matrix and woven bone. In on-study samples from 20 of 20 patients (100%), a decrease of 90% or more in tumor giant cells and a reduction in tumor stromal cells were observed. In these analyses, thirteen patients (65%) had an increased proportion of dense fibro-osseous tissue and/or new woven bone, replacing areas of proliferative RANKL-positive stromal cells.Conclusions: Denosumab treatment of patients with GCTB significantly reduced or eliminated RANKpositive tumor giant cells. Denosumab also reduced the relative content of proliferative, densely cellular tumor stromal cells, replacing them with nonproliferative, differentiated, densely woven new bone. Denosumab continues to be studied as a potential treatment for GCTB.

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“…The first is the mesenchymal stromal cell, which is of osteoblastic lineage as demonstrated by the expression of the osteoblastic markers osteopontin, osteocalcin, and osteonectin [5]. Furthermore, these cells are known to be the neoplastic element of the tumor, and they serve to regulate the tumor environment through the expression and secretion of the cytokine receptor activator of nuclear factor κB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) [6]. In bone, RANKL acts in concert with M-CSF to promote the proliferation and differentiation of monocytes (of macrophage lineage) into osteoclast-like multinucleated giant cells [6].…”

Section: Introductionmentioning

confidence: 99%