Importance of osteoprotegrin and receptor activator of nuclear factor kB in breast cancer response to hepatocyte growth factor and the bone microenvironment in vitro

Owen, Sioned, Sanders, Andrew J. ORCID: https://orcid.org/0000-0002-7997-5286, Mason, Malcolm David ORCID: https://orcid.org/0000-0003-1505-2869 and Jiang, Wen Guo ORCID: https://orcid.org/0000-0002-3283-1111 2016. Importance of osteoprotegrin and receptor activator of nuclear factor kB in breast cancer response to hepatocyte growth factor and the bone microenvironment in vitro. International Journal of Oncology 48 (3) , pp. 919-928. 10.3892/ijo.2016.3339

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Abstract

Osteoprotegrin (OPG), receptor activator of nuclear factor κB (RANK) and RANK ligand (RANKL) are signal transducers which have pleiotropic actions. Each tumour necrosis factor receptor superfamily member has unique structural attributes which directly couples them to signalling pathways involved in cell proliferation, differentiation and survival. Previous studies have clinically linked OPG, RANK and RANKL to increasing tumour burden, metastatic bone involvement and estrogen status. This study aimed to establish the potential implications of targeting endogenously produced OPG and RANK in the osteotropic breast cancer cell line MDA-MB‑231 in vitro. Subsequently this study also aimed to explore the potential links between these molecules with regards to hepatocyte growth factor (HGF) signalling and extracted bone proteins (BME). OPG and RANK expression was successfully suppressed using hammerhead ribozyme technology. Subsequently effects were explored in MDA-MB‑231 cell proliferation, matrix adhesion, migration and invasion in vitro function assays. Reduced OPG expression resulted in increased breast cancer cell migration and invasion. These increases, particularly invasion, appeared to however be reduced under the influence of the exogenous stimuli (HGF and BME). In contrast, suppression of RANK in MDA-MB‑231 breast cancer cells resulted in decreased cancer cell proliferation, matrix-adhesion, motility and invasion with little cumulative effect being noted after the addition of exogenous stimuli. The complexity of the bone environment underpins the vast number of soluble factors and signalling pathways which can influence osteotropic cancer behaviour and progression. Further work into elucidating all the pathways affected could potentially lead to better identification of those patients most at risk.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Publisher:	Spandidos Publications
ISSN:	1019-6439
Date of First Compliant Deposit:	30 March 2016
Date of Acceptance:	11 September 2015
Last Modified:	05 May 2023 08:11
URI:	https://orca.cardiff.ac.uk/id/eprint/86279

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