Overexpression of hypoxia-inducible factor-1α and vascular endothelial growth factor in sacral giant cell tumors and the correlation with tumor microvessel density

Fu, Shao-Feng; Bai, Rui; Zhao, Zhenqun; Zhang, Zhifeng; Zhang, Gang; Wang, Yuxin; Wang, Yong; Jiang, Dianming; Zhu, Daqi

doi:10.3892/etm.2014.1971

Cited by 8 publications

(13 citation statements)

References 38 publications

(35 reference statements)

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“…The primary antibodies were removed by washing with PBST, and the tissues were incubated with secondary IgG antibodies before staining with 3, 3-diaminobenzidine (DAB) and restaining with hematoxylin. The immunoreactivity of Nox4 in the vascular tunnel was visualized with high-resolution images of individual vessel walls using image analysis and a color-recognition algorithm of Image-Pro Plus 6.0, as previously described [ 22 , 23 ].…”

Section: Methodsmentioning

confidence: 99%

Key Role of ROS in the Process of 15-Lipoxygenase/15-Hydroxyeicosatetraenoiccid-Induced Pulmonary Vascular Remodeling in Hypoxia Pulmonary Hypertension

Mao

Qiu

et al. 2016

PLoS ONE

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We previously reported that 15-lipoxygenase (15-LO) and its metabolite 15-hydroxyeicosatetraenoic acid (15-HETE) were up-regulated in pulmonary arterial cells from both pulmonary artery hypertension patients and hypoxic rats and that these factors mediated the progression of pulmonary hypertension (PH) by affecting the proliferation and apoptosis of pulmonary arterial (PA) cells. However, the underlying mechanisms of the remodeling induced by 15-HETE have remained unclear. As reactive oxygen species (ROS) and 15-LO are both induced by hypoxia, it is possible that ROS are involved in the events of hypoxia-induced 15-LO expression that lead to PH. We employed immunohistochemistry, tube formation assays, bromodeoxyuridine (BrdU) incorporation assays, and cell cycle analyses to explore the role of ROS in the process of 15-HETE-mediated hypoxic pulmonary hypertension (HPH). We found that exogenous 15-HETE facilitated the generation of ROS and that this effect was mainly localized to mitochondria. In particular, the mitochondrial electron transport chain and nicotinamide-adenine dinucleotide phosphate oxidase 4 (Nox4) were responsible for the significant 15-HETE-stimulated increase in ROS production. Moreover, ROS induced by 15-HETE stimulated endothelial cell (EC) migration and promoted pulmonary artery smooth muscle cell (PASMC) proliferation under hypoxia via the p38 MAPK pathway. These results indicated that 15-HETE-regulated ROS mediated hypoxia-induced pulmonary vascular remodeling (PVR) via the p38 MAPK pathway.

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Section: Methodsmentioning

confidence: 99%

Key Role of ROS in the Process of 15-Lipoxygenase/15-Hydroxyeicosatetraenoiccid-Induced Pulmonary Vascular Remodeling in Hypoxia Pulmonary Hypertension

Mao

Qiu

et al. 2016

PLoS ONE

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“…LGALS3BP functions as a pro‐angiogenic factor through stimulating tumor VEGF expression and elevating endothelial cell tubulogenesis in breast cancer cells [Piccolo et al, ]. The elevated LGALS3BP in GCTB stromal cells may be associated with the increased VEGF expression and hyper‐vascularity observed in advanced GCTB [Kumta et al, ; Fu et al, ]. LGALS3BP also interacts with integrins α1β1, α5β1, αvβ1, and α6β1, and triggers multiple canonical “outside‐in” integrin signaling cascades including PI3 K/Akt, SAPK/JNK, and Raf/ERK pathways, which result in significantly increased cellular viability, motility and migration in melanoma cells [Stampolidis et al, ].…”

Section: Discussionmentioning

confidence: 99%

“…LGALS3BP functions as a pro-angiogenic factor through stimulating tumor VEGF expression and elevating endothelial cell tubulogenesis in breast cancer cells [Piccolo et al, 2013]. The elevated LGALS3BP in GCTB stromal cells may be associated with the increased VEGF expression and hypervascularity observed in advanced GCTB [Kumta et al, 2003;Fu et al, 2014].…”

Section: Discussionmentioning

confidence: 99%

Genome‐Wide Transcriptome Profiling of the Neoplastic Giant Cell Tumor of Bone Stromal Cells by RNA Sequencing

Lau¹,

Kwok

Tsui

et al. 2017

J of Cellular Biochemistry

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Giant cell tumor of bone (GCTB) is the most common non-malignant primary bone tumor reported in Hong Kong. Failure of treatment in advanced GCTB with aggressive local recurrence remains a clinical challenge. In order to reveal the molecular mechanism underlying the pathogenesis of this tumor, we aimed to examine the transcriptome profiling of the neoplastic stromal cells of GCTB in this study. RNA-sequencing was performed on three GCTB stromal cell samples and one bone marrow-derived MSC sample and 174 differentially expressed genes (DEGs) were identified between these two cell types. The top five up-regulated genes are SPP1, F3, TSPAN12, MMP13, and LGALS3BP and further validated by qPCR and Western Blotting. Knockdown of SPP1 was found to induce RUNX2 and OPG expression in GCTB stromal cells but not the MSCs. Ingenuity pathway analysis (IPA) of the 174 DEGs revealed significant alternations in 23 pathways; variant calling analysis revealed 1915 somatic variants of 384 genes with high or moderate impacts. Interestingly, four canonical pathways were found overlapping in both analyses; from which VEGFA, CSF1, PLAUR, and F3 genes with somatic mutation were found up-regulated in GCTB stromal cells. The STRING diagram showed two main clusters of the DEGs; one cluster of histone genes that are down-regulated in GCTB samples and another related to osteoblast differentiation, angiogenesis, cell cycle progression, and tumor growth. The DEGs and somatic mutations found in our study warrant further investigation and validation, nevertheless, our study add new insights in the search for new therapeutic targets in treating GCTB. J. Cell. Biochem. 118: 1349-1360, 2017. © 2016 Wiley Periodicals, Inc.

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“…GCT is a benign but very aggressive disease, with a rich blood supply and can present local invasion and further lung metastasis. 22 GCT contains over-proliferation of osteoclasts and numerous thin walled vascular channels predisposing to areas of hemorrhage and presumably related to the common co-existence of cystic regions. 11,[23][24][25] Microscopic observation also demonstrates a high microvessel density, and most microvascular structure is incomplete with irregular lumen, thin lumen wall, disorderly arranged, loss of endothelial cells in some vessel walls, and these will present as leaky vessels that have a high vascular permeability.…”

Section: Discussionmentioning

confidence: 99%

Morphological and dynamic contrast enhanced MR imaging features for the differentiation of chordoma and giant cell tumors in the Axial Skeleton

Xing

et al. 2016

Magnetic Resonance Imaging

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Purpose: To characterize the morphological and dynamic-contrast-enhanced (DCE) MRI features of chordoma and giant cell tumor (GCT) of bone occurring in the axial skeleton. Materials and Methods: A total of 13 patients with chordoma and 26 patients with GCT who received conventional T1, T2, and DCE-MRI on 3 Tesla MR scanners were retrospectively identified and analyzed. Two radiologists evaluated morphological features independently, including the lesion location, expansile bone changes, vertebral compression, presence of paraspinal soft tissue mass, fibrous septa, and the signal intensity on T1WI and T2WI. The inter-observer agreement was evaluated by kappa test. The DCE kinetics was measured to obtain the initial area under curve (IAUC) and the wash-out slope; also the two-compartmental pharmacokinetic model was applied to obtain Ktrans and kep. The diagnostic accuracy was evaluated by CHAID decision tree and ROC analysis. Results: Chordomas were more likely to show soft tissue mass than GCTs (13/13 = 100% versus 15/26 = 58%; P = 0.007), as well as fibrous septa (9/13 = 69% versus 0; P<0.001). In decision tree analysis, presence of fibrous septa and lesion location yield 31/39 = 79% accuracy. The DCE-MRI pharmacokinetic parameters Ktrans and kep of GCTs were significantly higher than those of chordomas, 0.136 0.65 versus 0.0660.04 (1/min) for Ktrans, 0.6260.22 versus 0.176 0.12 (1/min) for kep, P<0.001 for both. If using kep = 0.43/min as the cut-off value, it achieved 100% sensitivity and 92% specificity to differentiate chordoma from GCT, with an overall accuracy of 37/39 = 95%. The IAUC was highly correlated with Ktrans (r = 0.94), and the slope was highly correlated with kep (r = 0.95). Conclusion: Several morphological features were significantly different between chordoma and GCT, but their diagnostic performance was inferior to that of DCE-MRI.

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Overexpression of hypoxia-inducible factor-1α and vascular endothelial growth factor in sacral giant cell tumors and the correlation with tumor microvessel density

Cited by 8 publications

References 38 publications

Key Role of ROS in the Process of 15-Lipoxygenase/15-Hydroxyeicosatetraenoiccid-Induced Pulmonary Vascular Remodeling in Hypoxia Pulmonary Hypertension

Key Role of ROS in the Process of 15-Lipoxygenase/15-Hydroxyeicosatetraenoiccid-Induced Pulmonary Vascular Remodeling in Hypoxia Pulmonary Hypertension

Genome‐Wide Transcriptome Profiling of the Neoplastic Giant Cell Tumor of Bone Stromal Cells by RNA Sequencing

Morphological and dynamic contrast enhanced MR imaging features for the differentiation of chordoma and giant cell tumors in the Axial Skeleton

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