Endocrine Abstracts

Androgen ablation therapy remains the most common treatment for patients with advanced prostate cancer (PCa). However, most patients relapse and develop a castration-resistant PCa. The emergence of androgen receptor (AR) variants, such as constitutively active ARs, has been involved in this failure to androgen deprivation. Nevertheless, the tumour microenvironment is another necessary feature driving PCa progression. Cancer associated fibroblasts (CAFs) are one of the specialized stromal cells that favour tumour progression. They can be derived from different cell types, and 25% of CAFs originate from bone marrow-derived mesenchymal stem cells (MSCs). In this study, we investigated the effects of AR variants on the surrounding prostate tumour microenvironment by focusing on MSCs differentiation into CAFs. We used an in vitro co-culture system of human MSCs together with LNCaP cells, expressing or not AR variants, to analyse CAFs differentiation markers expression in MSCs by RT-qPCR. These differentiation markers were also analysed with a FISH approach in MSCs exposed to conditioned medium of LNCaP cells expressing or not AR variants. RT-qPCR data revealed an upregulation of several CAFs differentiation markers in MSCs such as FSP-1. These results were confirmed with a FISH approach showing an increase in FSP-1 fluorescent spot number for MSCs exposed to conditioned medium from LNCaP cells expressing AR variants. Together, our data would highlight an unknown property of AR variants in prostate tumour cells that is their ability to induce MSCs differentiation into CAFs. Studies are going on to validate these data using an in vivo PCa model.

Presenting author: Edwige Schreyer, INSERM U1113, Team 3 “Cell signalling and communication in kidney and prostate cancer”, University of Strasbourg, 1 Place de l’Hôpital, 67091, Strasbourg, France. Email: [email protected].