Cargando…

Farnesoid X receptor as marker of osteotropism of breast cancers through its role in the osteomimetism of tumor cells

BACKGROUND: The skeleton is the first and most common distant metastatic site for breast cancer. Such metastases complicate cancer management, inducing considerable morbidities and decreasing patient survival. Osteomimetism is part of the complex process of osteotropism of breast cancer cells. Recen...

Descripción completa

Detalles Bibliográficos
Autores principales: Absil, L., Journé, F., Larsimont, D., Body, J. J., Tafforeau, L., Nonclercq, D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7350202/
https://www.ncbi.nlm.nih.gov/pubmed/32650752
http://dx.doi.org/10.1186/s12885-020-07106-7
_version_ 1783557216776749056
author Absil, L.
Journé, F.
Larsimont, D.
Body, J. J.
Tafforeau, L.
Nonclercq, D.
author_facet Absil, L.
Journé, F.
Larsimont, D.
Body, J. J.
Tafforeau, L.
Nonclercq, D.
author_sort Absil, L.
collection PubMed
description BACKGROUND: The skeleton is the first and most common distant metastatic site for breast cancer. Such metastases complicate cancer management, inducing considerable morbidities and decreasing patient survival. Osteomimetism is part of the complex process of osteotropism of breast cancer cells. Recent data indicate that Farnesoid X Receptor (FXR) is involved in the transformation and progression of breast cancer. METHODS: The expression of FXR, Runt-related transcription factor 2 (RUNX2) and bone proteins were evaluated on two tumor cell lines (MCF-7 and MDA-MB-231) by immunohistochemistry, immunofluorescence and western blotting and quantified. RESULTS: In a series of 81 breast cancer patients who developed distant metastases, we found a strong correlation between FXR expression in primary breast tumors and the development of bone metastases, especially in patients with histological grade 3 tumors. In in vitro studies, FXR activation by Chenodeoxycholic acid (CDCA) increased the expression of numerous bone proteins. FXR inhibition by lithocholic acid and z-guggulsterone decreased bone protein expression. Short Hairpin RNA (ShRNA) against FXR validated the involvement of FXR in the osteomimetism of breast cancer cells. CONCLUSION: Our experimental results point to a relationship between the expression of FXR in breast cancer cells and the propensity of these tumor cells to develop bone metastases. FXR induces the expression of RUNX2 which itself causes the synthesis of bone proteins by tumor cells.
format Online
Article
Text
id pubmed-7350202
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-73502022020-07-14 Farnesoid X receptor as marker of osteotropism of breast cancers through its role in the osteomimetism of tumor cells Absil, L. Journé, F. Larsimont, D. Body, J. J. Tafforeau, L. Nonclercq, D. BMC Cancer Research Article BACKGROUND: The skeleton is the first and most common distant metastatic site for breast cancer. Such metastases complicate cancer management, inducing considerable morbidities and decreasing patient survival. Osteomimetism is part of the complex process of osteotropism of breast cancer cells. Recent data indicate that Farnesoid X Receptor (FXR) is involved in the transformation and progression of breast cancer. METHODS: The expression of FXR, Runt-related transcription factor 2 (RUNX2) and bone proteins were evaluated on two tumor cell lines (MCF-7 and MDA-MB-231) by immunohistochemistry, immunofluorescence and western blotting and quantified. RESULTS: In a series of 81 breast cancer patients who developed distant metastases, we found a strong correlation between FXR expression in primary breast tumors and the development of bone metastases, especially in patients with histological grade 3 tumors. In in vitro studies, FXR activation by Chenodeoxycholic acid (CDCA) increased the expression of numerous bone proteins. FXR inhibition by lithocholic acid and z-guggulsterone decreased bone protein expression. Short Hairpin RNA (ShRNA) against FXR validated the involvement of FXR in the osteomimetism of breast cancer cells. CONCLUSION: Our experimental results point to a relationship between the expression of FXR in breast cancer cells and the propensity of these tumor cells to develop bone metastases. FXR induces the expression of RUNX2 which itself causes the synthesis of bone proteins by tumor cells. BioMed Central 2020-07-10 /pmc/articles/PMC7350202/ /pubmed/32650752 http://dx.doi.org/10.1186/s12885-020-07106-7 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Article
Absil, L.
Journé, F.
Larsimont, D.
Body, J. J.
Tafforeau, L.
Nonclercq, D.
Farnesoid X receptor as marker of osteotropism of breast cancers through its role in the osteomimetism of tumor cells
title Farnesoid X receptor as marker of osteotropism of breast cancers through its role in the osteomimetism of tumor cells
title_full Farnesoid X receptor as marker of osteotropism of breast cancers through its role in the osteomimetism of tumor cells
title_fullStr Farnesoid X receptor as marker of osteotropism of breast cancers through its role in the osteomimetism of tumor cells
title_full_unstemmed Farnesoid X receptor as marker of osteotropism of breast cancers through its role in the osteomimetism of tumor cells
title_short Farnesoid X receptor as marker of osteotropism of breast cancers through its role in the osteomimetism of tumor cells
title_sort farnesoid x receptor as marker of osteotropism of breast cancers through its role in the osteomimetism of tumor cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7350202/
https://www.ncbi.nlm.nih.gov/pubmed/32650752
http://dx.doi.org/10.1186/s12885-020-07106-7
work_keys_str_mv AT absill farnesoidxreceptorasmarkerofosteotropismofbreastcancersthroughitsroleintheosteomimetismoftumorcells
AT journef farnesoidxreceptorasmarkerofosteotropismofbreastcancersthroughitsroleintheosteomimetismoftumorcells
AT larsimontd farnesoidxreceptorasmarkerofosteotropismofbreastcancersthroughitsroleintheosteomimetismoftumorcells
AT bodyjj farnesoidxreceptorasmarkerofosteotropismofbreastcancersthroughitsroleintheosteomimetismoftumorcells
AT tafforeaul farnesoidxreceptorasmarkerofosteotropismofbreastcancersthroughitsroleintheosteomimetismoftumorcells
AT nonclercqd farnesoidxreceptorasmarkerofosteotropismofbreastcancersthroughitsroleintheosteomimetismoftumorcells