Osteoprotegerin rich tumor microenvironment: implications in breast cancer

Goswami, Sudeshna; Sharma-Walia, Neelam

doi:10.18632/oncotarget.8658

Cited by 25 publications

(26 citation statements)

References 99 publications

(156 reference statements)

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“…Osteoprotegerin not only inhibits apoptosis, but it might also induce proliferation by binding to various cell surface receptors, including canonical cell survival and proliferative pathways. OPG also participates in the induction of angiogenesis, facilitating tumour growth [35].…”

Section: Discussionmentioning

confidence: 99%

Changes in the Concentration of Markers Participating in the Regulation of the Apoptosis Receptor Pathway Involving Soluble Tumour Necrosis Factor Ligand Inducing Apoptosis (sTRAIL) and Osteoprotegerin (OPG) in the Serum of Women with Ovarian Cancer—Participation in Pathogenesis or a Possible Clinical Use?

Mielczarek‐Palacz

Kondera-Anasz

Smycz‐Kubańska

2020

Cells

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Due to the ability to selectively induce apoptosis in cancer cells, the most interesting target for clinical research is the tumour necrosis factor ligand inducing apoptosis (TRAIL), which binds specific receptors, including osteoprotegerin (OPG). The aim of the study was to analyse the concentration of soluble TRAIL (sTRAIL) and OPG in the serum of women with serous or mucinous ovarian cancer, taking into account different levels of cancer histological differentiation. The group included 97 women with the diagnosed Cystadenocarcinoma papillare serosum IIIc and Cystadenocarcinoma mucinosum IIIc. Concentrations of parameters were measured by ELISA. Analysis of the obtained results showed a statistically significantly higher concentration of sTRAIL and OPG in the serum of women with ovarian serous and mucinous cancer compared to the control group (p < 0.0001). Statistical significance was found between sTRAIL and OPG concentration in G1 and G3 serous cancer (p < 0.01) and in OPG mucinous cancer between G1 and G3 (p < 0.01) and G2 and G3 (p < 0.01). An important role in the pathogenesis of ovarian cancer is played by disorders of the apoptosis process involving the sTRAIL/OPG system, which are associated with the histological type and the degree of histological differentiation of the tumour. Determining the concentration of tested parameters in combination with other markers may be useful in the future in the diagnosis of ovarian cancer, but that requires further research.

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Section: Discussionmentioning

confidence: 99%

Changes in the Concentration of Markers Participating in the Regulation of the Apoptosis Receptor Pathway Involving Soluble Tumour Necrosis Factor Ligand Inducing Apoptosis (sTRAIL) and Osteoprotegerin (OPG) in the Serum of Women with Ovarian Cancer—Participation in Pathogenesis or a Possible Clinical Use?

Mielczarek‐Palacz

Kondera-Anasz

Smycz‐Kubańska

2020

Cells

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“…and ours on the effect of OPG on patients’ survival may be attributable to differences in size and characteristics of the investigated collective and to the different methods used, and in particular to the utilization of immunohistochemistry to assess OPG in tissue specimens vs. ELISA-based assessment of OPG in serum. OPG has been shown to be expressed not only by cancer cells but also by cells of the tumor microenvironment, ([15, 16] and reviewed by Goswami and Sharma-Walia [9]); assessment of serum OPG has therefore the advantage of accounting for OPG deriving also from other sources than the tumour cells (e.g. blood vessels and immune cells [9]).…”

Section: Discussionmentioning

confidence: 99%

“…OPG has been shown to be expressed not only by cancer cells but also by cells of the tumor microenvironment, ([15, 16] and reviewed by Goswami and Sharma-Walia [9]); assessment of serum OPG has therefore the advantage of accounting for OPG deriving also from other sources than the tumour cells (e.g. blood vessels and immune cells [9]). Furthermore, measurement of OPG in serum is less influenced by the investigator-related variability of immunohistochemical investigation, and is likely more representative than immunohistochemical assessment of OPG in biopsies from single tumour lesions, which can be influenced by clonal effects and the tumour heterogeneity typical of late-stage tumours.…”

Section: Discussionmentioning

confidence: 99%

“…According to the proposed role of the TRAIL-system in oncogenesis, OPG is thought to contribute to the development of several tumour entities comprising breast, prostate and gastric cancer [6-8]. More recently, however, it has been proposed that OPG also affects other mechanisms of tumour formation, including enhancement of cell proliferation and paracrine mechanisms influencing tumour microenvironment [9]. …”

Section: Introductionmentioning

confidence: 99%

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Correlation Between Baseline Osteoprotegerin Serum Levels and Prognosis of Advanced-Stage Colorectal Cancer Patients

Toni

Nagel

Philipp

et al. 2018

Cell Physiol Biochem

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Background/Aims: Osteoprotegerin (OPG) is a soluble receptor of the pro-apoptotic cytokine TRAIL which is thought to contribute to tumour development by inhibiting apoptosis or affecting other aspects of tumour biology, including cell proliferation and immune response. Although immunohistochemical studies suggest that OPG correlates with survival in metastatic colorectal cancer (mCRC), only scarce data are available on serum OPG in CRC patients. Methods: In this pilot study, we assessed the prognostic significance of serum OPG and CEA (Carcinoembryonic antigen) in 81 patients with UICC (Union for International Cancer Control) stage-IV mCRC. OPG was additionally assessed by immunohistochemistry in primary tissue samples from 33 patients of the same cohort. Results: Baseline serum OPG correlated with CEA (r=0.36, p=0.0011), but independently predicted survival of mCRC patients. Life expectancy was poorer in patients with OPG levels above the median concentration of 51ng/ml (median overall survival [95% confidence interval] 1.8 years [1.3-3.0] vs. 1.0 [0.7-1.2] p=0.013). Patients with high levels of both OPG and CEA had an even poorer life expectancy vs. low-OPG/low-CEA patients (0.9 years [0.6-1.5] vs. 3 years [1.2-4.4], p=0.015), indicating that CEA and OPG have additive prognostic significance. Immunohistochemical analysis of OPG failed to show a correlation between OPG staining and survival (p=0.055) or OPG concentration from matched serum samples. Conclusions: This pilot study provides evidence of independent prognostic significance of serum OPG in patients with advanced mCRC and warrants its further prospective validation.

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“…DcR4/TNFRSF11B, also known as osteoprotegerin (OPG), acts as decoy receptor for TNFSF11/ RANKL and thereby neutralizes its function in osteoclastogenesis. TNFRSF11B may also act as a soluble decoy receptor for TNFSF10/TRAIL, plays an inhibitory role in TRAIL-induced cell apoptosis and protects against TRAIL-mediated apoptosis [57]. OPG was initially discovered to contribute to homeostasis of bone turnover due to its capability of binding to receptor activator of nuclear factor-κB (NF-kB), but apart from bone turnover, OPG plays important and diverse roles in many biological functions.…”

Section: Tumor Necrosis Factor-related Decoy Receptorsmentioning

confidence: 99%

The role of the TNF receptors and apoptosis inducing ligands in tumor growth

Minchenko¹,

Tsymbal²,

Minchenko³

et al. 2016

Ukr.Biochem.J.

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Tumor necrosis factor (TNF) superfamily receptors and TNF apoptosis inducing ligands play an important role in the realization of TNF function and control tumor growth. The TNF-related pathways are controlled by endoplasmic reticulum stress signaling, which has a crucial role in the control of cell proliferation and tumor growth. Furthermore, the inhibition of IRE1 (inositol requiring enzyme-1), which is a central mediator of endoplasmic reticulum stress sand mainly responsible for cell proliferation and apoptosis, leads to suppression of tumor growth through specific changes in the expression of genes encoding transcription factors, tumor suppressors, angiogenesis and apoptosis related proteins, including TNF superfamily receptors and TNF apoptosis inducing ligands. Therefore, changes in the expression level of TNF-related genes encoding TNF superfamily receptors and apoptosis inducing ligands possibly reflect metabolic reprogramming of cancer cells upon inhibition of IRE1-mediated endoplasmic reticulum stress signaling and correlate with suppression of glioma cell proliferation.

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Osteoprotegerin rich tumor microenvironment: implications in breast cancer

Cited by 25 publications

References 99 publications

Correlation Between Baseline Osteoprotegerin Serum Levels and Prognosis of Advanced-Stage Colorectal Cancer Patients

The role of the TNF receptors and apoptosis inducing ligands in tumor growth

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