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

[en] 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.

Disciplines :

Oncology
Biochemistry, biophysics & molecular biology

Author, co-author :

Absil, Lara ; Université de Mons > Faculté de Médecine et de Pharmacie > Service d'Histologie

Journe, Fabrice ; Université de Mons > Faculté de Médecine et de Pharmacie > Service d'Anatomie humaine et Oncologie expérimentale

Larsimont, Denis

Body, Jean-Jacques

Tafforeau, Lionel ; Université de Mons > Faculté des Sciences > Service de Biologie cellulaire

Nonclercq, Denis ; Université de Mons > Faculté de Médecine et de Pharmacie > Service d'Histologie

Language :

English

Title :

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

Publication date :

10 July 2020

Journal title :

BMC Cancer

eISSN :

1471-2407

Publisher :

BioMed Central, London, United Kingdom

Volume :

Pages :

640

Peer reviewed :

Peer Reviewed verified by ORBi

Research unit :

M112 - Anatomie humaine et Oncologie expérimentale
M118 - Histologie
S815 - Biologie cellulaire

Research institute :

R550 - Institut des Sciences et Technologies de la Santé
R100 - Institut des Biosciences

Available on ORBi UMONS :

since 16 October 2020

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