Harnessing the versatile role of OPG in bone oncology: counterbalancing RANKL and TRAIL signaling and beyond

Deligiorgi, Maria V; Panayiotidis, Mihalis Ι.; Grınıatsos, John; Trafalis, Dimitrios T.

doi:10.1007/s10585-019-09997-8

Cited by 23 publications

(18 citation statements)

References 127 publications

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“…In addition, their predominant presence in osteoid-matrix forming tumor regions-the most frequent type of OS-indicates that administration of ZA is not the best therapeutic strategy. Even if the therapeutic value of a bisphosphonate or anti-RANKL antibody treatment is limited in OS, these drugs have proven their value in the treatment of osteolytic metastasis [17,51] and could be further proposed to the rare cases presenting highly osteolytic OS, characterized by high TRAP level in serum at diagnosis. Levels of the circulating RANKL marker, considered to be the most accurate marker for the evaluation of metastatic bone response [53], could then be useful in assessing the efficacy of such treatments in OS.…”

Section: Discussionmentioning

confidence: 99%

“…Osteosarcoma (OS) is the most common primary malignant bone tumor [1] and has a worldwide incidence of one to three cases per million annually with a higher incidence in teenagers (0.8-1.1/100,000/year for ages [15][16][17][18][19]. Conventional OS is the most common histologic subtype (75% of all cases) [1,2].…”

Section: Introductionmentioning

confidence: 99%

“…The pivotal role played by the bone Tumor Micro-Environment (TME) has been suggested for many years in OS [17][18][19]. The bone microenvironment is very complex, with a finely balanced interplay between osteoblasts, osteoclasts, chondrocytes, mesenchymal stem/progenitor cells, hematopoietic cells, endothelial cells, and others [20].…”

Section: Introductionmentioning

confidence: 99%

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Characterization of Macrophages and Osteoclasts in the Osteosarcoma Tumor Microenvironment at Diagnosis: New Perspective for Osteosarcoma Treatment?

Gomez‐Brouchet

Gilhodes

Acker

et al. 2021

Cancers

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Biological and histopathological techniques identified osteoclasts and macrophages as targets of zoledronic acid (ZA), a therapeutic agent that was detrimental for patients in the French OS2006 trial. Conventional and multiplex immunohistochemistry of microenvironmental and OS cells were performed on biopsies of 124 OS2006 patients and 17 surgical (“OSNew”) biopsies respectively. CSF-1R (common osteoclast/macrophage progenitor) and TRAP (osteoclast activity) levels in serum of 108 patients were correlated to response to chemotherapy and to prognosis. TRAP levels at surgery and at the end of the protocol were significantly lower in ZA+ than ZA− patients (padj = 0.0011; 0.0132). For ZA+-patients, an increase in the CSF-1R level between diagnosis and surgery and a high TRAP level in the serum at biopsy were associated with a better response to chemotherapy (p = 0.0091; p = 0.0251). At diagnosis, high CD163+ was associated with good prognosis, while low TRAP activity was associated with better overall survival in ZA− patients only. Multiplex immunohistochemistry demonstrated remarkable bipotent CD68+/CD163+ macrophages, homogeneously distributed throughout OS regions, aside osteoclasts (CD68+/CD163−) mostly residing in osteolytic territories and osteoid-matrix-associated CD68−/CD163+ macrophages. We demonstrate that ZA not only acts on harmful osteoclasts but also on protective macrophages, and hypothesize that the bipotent CD68+/CD163+ macrophages might present novel therapeutic targets.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Characterization of Macrophages and Osteoclasts in the Osteosarcoma Tumor Microenvironment at Diagnosis: New Perspective for Osteosarcoma Treatment?

Gomez‐Brouchet

Gilhodes

Acker

et al. 2021

Cancers

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“…Recent research has shown that TNFRSF11B is involved in the development and progression of several human malignancies [13][14][15][16][17][18][19][20][21]. In gastric cancer, high expression of TNFRSF11B was found in gastric cancer cell lines, primary cancer and bone metastasis tissues.…”

Section: Ivyspringmentioning

confidence: 99%

TNFRSF11B activates Wnt/β-catenin signaling and promotes gastric cancer progression

Luan¹,

Li²,

Cheng³

et al. 2020

Int. J. Biol. Sci.

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Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B) has been studied to be involved in the development and progression of several human malignancies. However, little is unveiled regarding the complex mechanisms of TNFRSF11B in human gastric cancer (GC). The clinical significance of TNFRSF11B was assessed in 70 and 160 GC tissues using immunohistochemistry method and gene microarray analysis, respectively. The biological function of TNFRSF11B was studied in vitro and in vivo assays. Immunofluorescence assay was used to evaluate the expression of β-catenin in the nucleus. The expression of β-catenin and related protein was determined by Western blot. The interaction between TNFRSF11B and GSK3β was detected by co-immunoprecipitation. We demonstrated that TNFRSF11B was highly expressed in the cytoplasm of GC and associated with the patient poor outcome. Our studies showed that TNFRSF11B in GC cells significantly promoted cell proliferation, migration, invasion in vitro and tumorigenic ability in vitro and in vivo. Meanwhile, TNFRSF11B inhibited GC cell apoptosis. The proportion of nuclear active β-catenin showed positively correlation with TNFRSF11B expression. TNFRSF11B directly combined with GSK-3β upregulating its phosphorylation, and increased expression of β-catenin and its downstream effectors. Collectively, these findings demonstrate that TNFRSF11B promote the aggressive phenotypes of GC cells and activated Wnt/β-catenin signaling. Accordingly, TNFRSF11B had potential as a biomarker and inhibition of TNFRSF11B expression might offer a new therapeutic target for GC patients.

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“…The combination and interaction between RANKL and RANK could induce osteoclastogenesis, while OPG competes with RANK to bind RANKL, thereby inhibiting the formation of osteoclasts and bone resorption [ 49 ]. As such, a low ratio of RANKL/OPG is generally regarded as the mark of osteogenesis [ 50 , 51 ]. Lu et al [ 19 ] found that OVX-rBMSCs seeded on the Ta sheets exhibited lower expression of RANKL and higher expression of OPG than that of the Ti group at mRNA level, indicating the osteogenesis potential of Ta through OPG/RANKL/RANK signaling pathway.…”

Section: Osteogenesis Signaling Pathways Related To Tamentioning

confidence: 99%

From the Performance to the Essence: The Biological Mechanisms of How Tantalum Contributes to Osteogenesis

Lei

et al. 2020

BioMed Research International

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Despite the brilliant bioactive performance of tantalum as an orthopedic biomaterial verified through laboratory researches and clinical practice in the past decades, scarce evidences about the essential mechanisms of how tantalum contributes to osteogenesis were systematically discussed. Up to now, a few studies have uncovered preliminarily the biological mechanism of tantalum in osteogenic differentiation and osteogenesis; it is of great necessity to map out the panorama through which tantalum contributes to new bone formation. This minireview summarized current advances to demonstrate the probable signaling pathways and underlying molecular cascades through which tantalum orchestrates osteogenesis, which mainly contain Wnt/β-catenin signaling pathway, BMP signaling pathway, TGF-β signaling pathway, and integrin signaling pathway. Limits of subsistent studies and further work are also discussed, providing a novel vision for the study and application of tantalum.

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Harnessing the versatile role of OPG in bone oncology: counterbalancing RANKL and TRAIL signaling and beyond

Cited by 23 publications

References 127 publications

Characterization of Macrophages and Osteoclasts in the Osteosarcoma Tumor Microenvironment at Diagnosis: New Perspective for Osteosarcoma Treatment?

Characterization of Macrophages and Osteoclasts in the Osteosarcoma Tumor Microenvironment at Diagnosis: New Perspective for Osteosarcoma Treatment?

TNFRSF11B activates Wnt/β-catenin signaling and promotes gastric cancer progression

From the Performance to the Essence: The Biological Mechanisms of How Tantalum Contributes to Osteogenesis

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