scholarly journals New Target for Precision Medicine Treatment of Giant-Cell Tumor of Bone: Sunitinib Is Effective in the Treatment of Neoplastic Stromal Cells with Activated PDGFRβ Signaling

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3543
Author(s):  
Michal Mahdal ◽  
Jakub Neradil ◽  
Peter Mudry ◽  
Silvia Paukovcekova ◽  
Iva Staniczkova Zambo ◽  
...  
Keyword(s):  
Growth Factor ◽  
Giant Cell Tumor ◽  
Giant Cell ◽  
Stromal Cells ◽  
Growth Factor Receptor ◽  
Metastatic Potential ◽  
Giant Cells ◽  
Cell Tumor ◽  
Primary Bone Tumor

Giant-cell tumor of bone (GCTB) is an intermediate type of primary bone tumor characterized by locally aggressive growth with metastatic potential. The aim of this study was to identify new druggable targets among the cell signaling molecules involved in GCTB tumorigenesis. Profiles of activated signaling proteins in fresh-frozen tumor samples and tumor-derived cell lines were determined using phosphoprotein arrays. Analysis of the obtained data revealed epidermal growth factor receptor (EGFR) and platelet-derived growth factor receptor beta (PDGFRβ) as potential targets, but only the PDGFR inhibitor sunitinib caused a considerable decrease in stromal cell viability in vitro. Furthermore, in the case of a 17-year-old patient suffering from GCTB, we showed that the addition of sunitinib to the standard treatment of GCTB with the monoclonal antibody denosumab resulted in the complete depletion of multinucleated giant cells and mononuclear stromal cells in the tumor tissue. To summarize, the obtained data showed that a specific receptor tyrosine kinase (RTK) signaling pattern is activated in GCTB cells and plays an important role in the regulation of cell proliferation. Thus, activated RTKs and their downstream signaling pathways represent useful targets for precision treatment with low-molecular-weight inhibitors or with other types of modern biological therapy.

scholarly journals Giant cell tumor stromal cells: osteoblast lineage-derived cells secrete IL-6 and IL-10 for M2 macrophages polarization

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9748
Author(s):  
Kuan Yang ◽  
Lihui Bao ◽  
Xiaoning He ◽  
Wanmin Zhao ◽  
Dongdong Fei ◽  
...  
Keyword(s):  
Giant Cell Tumor ◽  
Giant Cell ◽  
Stromal Cells ◽  
Macrophage Polarization ◽  
Giant Cells ◽  
Interleukin 10 ◽  
Cell Tumor ◽  
M2 Macrophages ◽  
M2 Polarization ◽  
Macrophages Polarization

Background The giant cell tumor (GCT) is a benign tumor which consists of three types cells: mononuclear histiocytic cells (MNHCs), multinuclear giant cells (MNGCs), and GCT stromal cells (GCTSCs). Numerous studies claim that GCTSCs have mesenchymal stem cells (MSCs) characters and play an important role in osteoclastogenesis; however, there are no research studies concerning macrophage polarization among GCT, which can be regarded as an ingredient for tumor aggression. Method We tested the effect of GCTSCs from three GCT samples which were collected from patients on proliferation, apoptosis and polarization of macrophage. Result In this article, we verified that GCTSCs expressed MSCs markers and had higher proliferation and relative lower differentiation abilities compared with BMMSCs. What’s more, we found a higher proportion of M2 macrophages among neoplasm. Co-culturing GCTSCs with macrophages resulted in prominent macrophage M2 polarization and increased the release of IL-6 (Interleukin-6) and IL-10 (Interleukin-10)from GCTSCs. In conclusion, GCTSCs, as originating from MSCs, can secret IL-6 and IL-10, which may play a significant role in macrophage M2 polarization.

Histomorphometric Analysis of Pre- and Post-Denosumab–Treated Giant Cell Tumor of Bone

2020 ◽  
Vol 28 (8) ◽  
pp. 859-867
Author(s):  
Nasir Ud Din ◽  
Masood Umer ◽  
Yong-Koo Park
Keyword(s):  
Giant Cell Tumor ◽  
Giant Cell ◽  
Stromal Cells ◽  
Mononuclear Cells ◽  
Giant Cells ◽  
Cell Tumor ◽  
P Value ◽  
Osteoblastic Activity ◽  
Woven Bone ◽  
Hematoxylin And Eosin

Context. Denosumab is a monoclonal antibody against RANK ligand. Its administration in giant cell tumor of bone (GCTB) cases results in elimination of giant cells and new bone formation. Neoplastic stromal cells of GCTB harbor mutation of histone 3.3 and have pre-osteoblastic properties and thus express SATB2. Objectives. To (1) analyze histological changes in post-denosumab–treated GCTB, (2) analyze expression of H3.3G34W and SATB2 in pre- and post-denosumab–treated samples, and (3) to discuss why changes occur in the expression of not only H3.3G34W but also SATB2. Materials and Methods. Hematoxylin and eosin slides of 19 cases of denosumab-treated GCTB were reviewed. Immunohistochemical stains H3.3G34W and SATB2 were performed. The number of positive mononuclear cells were counted and graded. Results. Complete absence of osteoclast-like giant cells (OCLGCs) was noted in most cases along with a fibro-osseous component merging with peripheral shell of reactive bone. Irregular trabeculae of woven bone and osteoid with focal osteoblastic rimming was seen. Spindle cells were arranged predominantly in fascicular pattern. Morphometric analysis of H3.3G34W showed a mean of 68.8% positive stromal cells in pretreatment and a mean of 26.9% positive stromal cells in posttreated specimens with a statistically significant P value (.001). Mean percentage of SATB2-positive stromal cells in the pre- and posttreatment specimens was 36.46% and 20.8%, respectively. Conclusions. Our study validates that denosumab treatment results in marked reduction of OCLGCs with increased osteoblastic activity. Decreased expression of H3.3G34W in posttreatment may be a result of decreased antigenicity of neoplastic mononuclear cells. No significant change in SATB2 expression was noted.

Giant Cell Tumor of Bone: A Model for the in Vitro Human Osteoclast Characterization

1989 ◽  
Vol 75 (4) ◽  
pp. 389-395 ◽  
Author(s):  
Mario Campanacci ◽  
Gian Paolo Bagnara ◽  
Massimo Serra ◽  
Marco Giovannini ◽  
Paolo Tornasi ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Giant Cell Tumor ◽  
Giant Cell ◽  
Giant Cells ◽  
Cell Tumor ◽  
Cell Populations ◽  
In Vitro Growth ◽  
Human Osteoclast ◽  
High Doses

The in vitro growth pattern of cells obtained from bioptic material of ten patients with giant cell tumor of bone (GCT) was investigated. Cytochemical reactions and monoclonal antibodies raised against macrophage markers were tested on the two histologically identifiable GCT cell populations. Only monoclonal antibody EBM/11 stained both mononuclear and giant cells. EBM/11 positivity and resistance of acid phosphatase to high doses of tartrate strongly suggest that both mononuclear and giant cells belong to the same lineage.

scholarly journals The Role of TWIST in Angiogenesis and Cell Migration in Giant Cell Tumor of Bone

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Shalini Singh ◽  
Isabella W. Y. Mak ◽  
Divya Handa ◽  
Michelle Ghert
Keyword(s):  
Cell Migration ◽  
Giant Cell Tumor ◽  
Giant Cell ◽  
Stromal Cells ◽  
Epithelial Mesenchymal Transition ◽  
Cell Tumor ◽  
Stable Cell Line ◽  
Mesenchymal Transition

Giant cell tumor of bone (GCT) is a bone tumor consisting of numerous multinucleated osteoclastic giant cells involved in bone resorption and neoplastic osteoblast-like stromal cells responsible for tumor growth. The tumor occasionally metastasizes to the lung; however, factors leading to metastasis in this tumor are unknown. The TWIST-1 protein (also referred to as TWIST) has been suggested to be involved in epithelial-mesenchymal transition (EMT) and tumor progression in some cancers. In this study we investigated the functional role of TWIST in GCT cell angiogenesis and migration. Overexpression of TWIST in neoplastic GCT stromal cells significantly increased mRNA and protein expression of VEGF and VEGFR1 in vitro, whereas knockdown of TWIST resulted in decreased VEGF and VEGFR1 expression. A stable cell line with TWIST overexpression resulted in features of EMT including increased cell migration and downregulation of E-cadherin. The results of our study indicate that TWIST may play an important role in angiogenesis and cell migration in GCT.

scholarly journals Denosumab Therapy Obscures Histological Features of Giant Cell Tumor of Bone

2019 ◽  
Vol 78 (12) ◽  
pp. 1171-1173
Author(s):  
Ahmed Gilani ◽  
Bette K Kleinschmidt-DeMasters
Keyword(s):  
Giant Cell Tumor ◽  
Giant Cell ◽  
Spindle Cell ◽  
Clinical History ◽  
Metastatic Potential ◽  
Giant Cells ◽  
Cell Tumor ◽  
Spindle Cell Sarcoma ◽  
Current Case ◽  
Histological Features

Abstract Giant cell tumor (GCT) of bone is a locally aggressive tumor with low metastatic potential, usually originating in long bones. Numerous spinal examples have been reported and thus GCTs can be encountered by neuropathologists. We describe a 69-year-old man with more than a 10-year history of GCT primary to the femur that had recently metastasized to the occipital skull bone. The patient had been receiving denosumab, an adjuvant therapy for GCT, prior to the metastasis. Review of the histological features of the original primary tumor in the femur showed archetypal features of GCT, but the posttreatment occipital skull metastasis showed a predominantly low-to-medium cell density spindle cell tumor with complete depletion of osteoclastic giant cells. Although this effect of the drug is increasingly being recognized by soft tissue pathologists, the current case illustrates the potentially confusing histology of postdenosumab-treated GCT for neuropathologists. The absence of giant cells leads the posttherapy primary or metastatic lesion to show histologic similarity to a multitude of benign and malignant fibro-osseous lesions or spindle cell sarcoma and highlights the importance of eliciting appropriate clinical history.

scholarly journals Successful Intravascular Correction of Intratumoral Pseudoaneurysm by Erosion of the Aorta in a Patient with Thoracic Giant Cell Tumor of Bone Responding to Denosumab

2015 ◽  
Vol 2015 ◽  
pp. 1-5
Author(s):  
Natalia M. P. Fraile ◽  
Diego Toloi ◽  
Ceci O. Kurimori ◽  
Adriana R. B. Matutino ◽  
Alberto Codima ◽  
...  
Keyword(s):  
Giant Cell Tumor ◽  
Giant Cell ◽  
Stromal Cells ◽  
Giant Cells ◽  
Cell Tumor ◽  
Significant Activity ◽  
Receptor Activator ◽  
Endovascular Approach ◽  
Nuclear Factor Kb ◽  
Recent Demonstration

Giant cell tumor of bone (GCT) is a rare, locally aggressive neoplasm characterized by the presence of giant cells with osteoclast activity. Its biology involves the overexpression of theReceptor Activator of Nuclear Factor kB Ligand(RANKL) by osteoclast-like giant cells and tumor stromal cells, which has been shown to be an actionable target in this disease. In cases amenable to surgical resection, very few therapeutic options were available until the recent demonstration of significant activity of the anti-RANK-ligand monoclonal antibody denosumab. Here we present a case of a patient with advanced GCT arising in the spine, recurring after multiple resections and embolization. Following initiation of denosumab, which resulted in unequivocal clinical improvement, computed tomography of the chest done for reassessment purposes revealed an intratumoral pseudoaneurysm by erosion of the aorta, further corrected by endovascular approach and stent placement. Patient had an unremarkable recovery from the procedure and continued benefit from therapy with denosumab and remains on treatment 24 months after the first dose.

Influence of Surface Chemistry on the Biological Feature of Giant Cell Tumor of Bone Stromal Cells In Vitro

2013 ◽  
Vol 3 (5) ◽  
pp. 554-563 ◽  
Author(s):  
Li-Hua Li ◽  
Ying-Hu Deng ◽  
Jin He ◽  
Guo-Bo Lan ◽  
Mei Li ◽  
...  
Keyword(s):  
Surface Chemistry ◽  
Giant Cell Tumor ◽  
Giant Cell ◽  
Stromal Cells ◽  
Cell Tumor ◽  
Biological Feature

Giant cell tumor of the calvaria in a child

1994 ◽  
Vol 80 (1) ◽  
pp. 148-151 ◽  
Author(s):  
Lee Reed ◽  
Crystl D. Willison ◽  
Sydney S. Schochet ◽  
Joseph L. Voelker
Keyword(s):  
Giant Cell Tumor ◽  
Giant Cell ◽  
Stromal Cells ◽  
Giant Cells ◽  
Cellular Tissue ◽  
Cell Tumor ◽  
Content Type ◽  
History Of ◽  
Rare Lesion ◽  
Fine Print

✓ A giant cell tumor involving the vertex of the skull is described in a 3-year-old child with no history of head trauma. The mass was present approximately 4 months prior to resection. Microscopically, the lesion consisted of highly cellular tissue composed of oval to spindle-shaped stromal cells admixed with numerous multinucleated giant cells. Giant cell tumor of the skull is a rare lesion, usually involving the sphenoid or temporal bone in adults. The differential diagnosis is discussed with reference to the literature regarding giant cell lesions, especially of the cranium. The authors are unaware of previous reports of a similar lesion in this location in such a young child.

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