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.

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.

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.

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