Osteoprotegerin Rich Tumor Microenvironment: Implications in Breast Cancer

Overview

Journal Oncotarget

Specialty Oncology

Date 2016 Apr 14

PMID 27072583

Citations 15

Authors

Sudeshna Goswami

Neelam Sharma-Walia

Affiliations

Soon will be listed here.

Abstract

Osteoprotegerin (OPG) is a soluble decoy receptor for tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL). It belongs to the tumor necrosis factor receptor superfamily (TNFRSF). OPG was initially discovered to contribute to homeostasis of bone turnover due to its capability of binding to receptor activator of nuclear factor-kappaB (NF-kB). However, apart from bone turnover, OPG plays important and diverse role(s) in many biological functions. Besides having anti-osteoclastic activity, OPG is thought to exert a protective anti-apoptotic action in OPG-expressing tumors by overcoming the physiologic mechanism of tumor surveillance exerted by TRAIL. Along with inhibiting TRAIL induced apoptosis, it can induce proliferation by binding to various cell surface receptors and thus turning on the canonical cell survival and proliferative pathways. OPG also induces angiogenesis, one of the hallmarks of cancer, thus facilitating tumor growth. Recently, the understanding of OPG and its different roles has been augmented substantially. This review is aimed at providing a very informative overview as to how OPG affects cancer progression especially breast cancer.

Citing Articles

The Role of Osteoprotegerin in Breast Cancer: Genetic Variations, Tumorigenic Pathways, and Therapeutic Potential.

Radhi J, El-Hagrasy A, Almosawi S, Alhashel A, Butler A Cancers (Basel). 2025; 17(3).

PMID: 39941709 PMC: 11815763. DOI: 10.3390/cancers17030337.

Osteoprotegerin, Parathyroid Hormone and Vitamin D as Effective Factors on Serum-Urine Calcium Levels in Breast Cancer Patients.

Jasim A, Mahmoud Eltayef E Arch Razi Inst. 2023; 77(5):1975-1986.

PMID: 37123149 PMC: 10133599. DOI: 10.22092/ARI.2022.358485.2226.

Osteoprotegerin (OPG) Upregulation Activates Breast Stromal Fibroblasts and Enhances Their Pro-Carcinogenic Effects through the STAT3/IL-6 Signaling.

Al-Nasrallah H, Al-Ansari M, Aboussekhra A Cells. 2022; 11(21).

PMID: 36359766 PMC: 9655455. DOI: 10.3390/cells11213369.

Salubrinal Exposes Anticancer Properties in Inflammatory Breast Cancer Cells by Manipulating the Endoplasmic Reticulum Stress Pathway.

Alsterda A, Asha K, Powrozek O, Repak M, Goswami S, Dunn A Front Oncol. 2021; 11:654940.

PMID: 34094947 PMC: 8173155. DOI: 10.3389/fonc.2021.654940.

Expression of receptor activator of NFkB (RANK) drives stemness and resistance to therapy in ER+HER2- breast cancer.

Gomes I, de Almeida B, Damaso S, Mansinho A, Correia I, Henriques S Oncotarget. 2020; 11(19):1714-1728.

PMID: 32477461 PMC: 7233807. DOI: 10.18632/oncotarget.27576.

References

Deodhar A, Dore R, Mandel D, Schechtman J, Shergy W, Trapp R . Denosumab-mediated increase in hand bone mineral density associated with decreased progression of bone erosion in rheumatoid arthritis patients. Arthritis Care Res (Hoboken). 2010; 62(4):569-74. DOI: 10.1002/acr.20004. View

Thomas R, Guise T, Yin J, Elliott J, Horwood N, Martin T . Breast cancer cells interact with osteoblasts to support osteoclast formation. Endocrinology. 1999; 140(10):4451-8. DOI: 10.1210/endo.140.10.7037. View

Mosheimer B, Kaneider N, Feistritzer C, Djanani A, Sturn D, Patsch J . Syndecan-1 is involved in osteoprotegerin-induced chemotaxis in human peripheral blood monocytes. J Clin Endocrinol Metab. 2005; 90(5):2964-71. DOI: 10.1210/jc.2004-1895. View

Mundy G . Metastasis to bone: causes, consequences and therapeutic opportunities. Nat Rev Cancer. 2002; 2(8):584-93. DOI: 10.1038/nrc867. View

Widschwendter M, Burnell M, Fraser L, Rosenthal A, Philpott S, Reisel D . Osteoprotegerin (OPG), The Endogenous Inhibitor of Receptor Activator of NF-κB Ligand (RANKL), is Dysregulated in BRCA Mutation Carriers. EBioMedicine. 2015; 2(10):1331-9. PMC: 4634624. DOI: 10.1016/j.ebiom.2015.08.037. View

Shi W, Qiu W, Wang W, Zhou X, Zhong X, Tian G . Osteoprotegerin is up-regulated in pancreatic cancers and correlates with cancer-associated new-onset diabetes. Biosci Trends. 2015; 8(6):322-6. DOI: 10.5582/bst.2014.01092. View

ORegan N, Moxon C, Gegenbauer K, OSullivan J, Chion A, Smith O . Marked elevation in plasma osteoprotegerin constitutes an early and consistent feature of cerebral malaria. Thromb Haemost. 2016; 115(4):773-80. PMC: 4990170. DOI: 10.1160/TH15-10-0796. View

Toffoli B, Bernardi S, Candido R, Sabato N, Carretta R, Corallini F . Osteoprotegerin induces morphological and functional alterations in mouse pancreatic islets. Mol Cell Endocrinol. 2010; 331(1):136-42. DOI: 10.1016/j.mce.2010.08.019. View

Erard M, Belenguer P, Caizergues-Ferrer M, Pantaloni A, Amalric F . A major nucleolar protein, nucleolin, induces chromatin decondensation by binding to histone H1. Eur J Biochem. 1988; 175(3):525-30. DOI: 10.1111/j.1432-1033.1988.tb14224.x. View

10.

Nakashima T, Kobayashi Y, Yamasaki S, Kawakami A, Eguchi K, Sasaki H . Protein expression and functional difference of membrane-bound and soluble receptor activator of NF-kappaB ligand: modulation of the expression by osteotropic factors and cytokines. Biochem Biophys Res Commun. 2000; 275(3):768-75. DOI: 10.1006/bbrc.2000.3379. View

11.

Tsukamoto S, Ishikawa T, Iida S, Ishiguro M, Mogushi K, Mizushima H . Clinical significance of osteoprotegerin expression in human colorectal cancer. Clin Cancer Res. 2011; 17(8):2444-50. DOI: 10.1158/1078-0432.CCR-10-2884. View

12.

Nyambo R, Cross N, Lippitt J, Holen I, Bryden G, Hamdy F . Human bone marrow stromal cells protect prostate cancer cells from TRAIL-induced apoptosis. J Bone Miner Res. 2004; 19(10):1712-21. DOI: 10.1359/JBMR.040703. View

13.

Ney J, Juhasz-Boess I, Gruenhage F, Graeber S, Bohle R, Pfreundschuh M . Genetic polymorphism of the OPG gene associated with breast cancer. BMC Cancer. 2013; 13:40. PMC: 3563620. DOI: 10.1186/1471-2407-13-40. View

14.

Wright H, McCarthy H, Middleton J, Marshall M . RANK, RANKL and osteoprotegerin in bone biology and disease. Curr Rev Musculoskelet Med. 2009; 2(1):56-64. PMC: 2684955. DOI: 10.1007/s12178-009-9046-7. View

15.

Kwan J, Hsu Y, Cheung C, Dupuis J, Saint-Pierre A, Eriksson J . Meta-analysis of genome-wide association studies identifies two loci associated with circulating osteoprotegerin levels. Hum Mol Genet. 2014; 23(24):6684-93. PMC: 4240210. DOI: 10.1093/hmg/ddu386. View

16.

Al-Faham Z, Al-Katib S, Jaiyesimi I, Bhavnagri S . Evaluation of a Case of Inflammatory Breast Cancer with 18F-FDG PET/CT. J Nucl Med Technol. 2015; 43(4):289-91. DOI: 10.2967/jnmt.114.148494. View

17.

Chanda D, Isayeva T, Kumar S, Siegal G, Szafran A, Zinn K . Systemic osteoprotegerin gene therapy restores tumor-induced bone loss in a therapeutic model of breast cancer bone metastasis. Mol Ther. 2008; 16(5):871-8. DOI: 10.1038/mt.2008.48. View

18.

Parzych K, Chinn T, Chen Z, Loaiza S, Porsch F, Valbuena G . Inadequate fine-tuning of protein synthesis and failure of amino acid homeostasis following inhibition of the ATPase VCP/p97. Cell Death Dis. 2016; 6:e2031. PMC: 4720905. DOI: 10.1038/cddis.2015.373. View

19.

Cross S, Yang Z, Brown N, Balasubramanian S, Evans C, Woodward J . Osteoprotegerin (OPG)--a potential new role in the regulation of endothelial cell phenotype and tumour angiogenesis?. Int J Cancer. 2005; 118(8):1901-8. DOI: 10.1002/ijc.21606. View

20.

Tsuda E, Goto M, Mochizuki S, Yano K, Kobayashi F, Morinaga T . Isolation of a novel cytokine from human fibroblasts that specifically inhibits osteoclastogenesis. Biochem Biophys Res Commun. 1997; 234(1):137-42. DOI: 10.1006/bbrc.1997.6603. View