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2020-07-10 - Article/Dans un journal avec peer-review - Anglais - 15 page(s)

Absil Lara , Journe Fabrice , Larsimont Denis, Body Jean-Jacques, Tafforeau Lionel , Nonclercq Denis , "Farnesoid X receptor as marker of osteotropism of breast cancers through its role in the osteomimetism of tumor cells" in BMC Cancer, 20, 640, https://doi.org/10.1186/s12885-020-07106-7

  • Edition : BioMed Central, London (United Kingdom)
  • Codes CREF : Biologie (DI3100), Cancérologie (DI3349)
  • Unités de recherche UMONS : Anatomie et Biologie cellulaire (M112), Histologie (M118), Biologie cellulaire (S815)
  • Instituts UMONS : Institut des Sciences et Technologies de la Santé (Santé), Institut des Biosciences (Biosciences)
Texte intégral :

Abstract(s) :

(Anglais) 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.