1958P - Influence of androgen deprivation therapy (ADT) on epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) features in prostate cancer (PCa)

Background

ADT is an established treatment for PCa, influencing different aspects of tumor biology. The study aimed to assess expression of EMT (E- and N-cadherins (cad)) and CSC (CD44, CD133) markers as well as androgen (AR) and estrogen (ERα, ERβ) receptors and transforming growth factor beta type II receptor (TβRII) (an EMT regulator) in localized PCa samples after ADT.

Methods

56 radical prostatectomy cases were analyzed. 15 of them had 3-6 months of ADT before surgery. Double immunofluorescent staining was used. For E-cad and CD44 staining intensity was assessed, for CD133 – presence of staining, for N-cad– weighed staining index (WSI) and for AR, ERα, ERβ and TβRII – total staining scores (TSS) per case.

Results

In the studied cohort expression of EMT and CSC markers didn’t differ significantly in cases after ADT and without it (p_χ2=0.71 for CD133, p_Mann-Whitney>0,05 for all other markers), that may assume that at least at the early stage of PCa development short-term ADT doesn’t influence these phenotypes. AR and ER expression both in stroma and epithelium didn’t differ significantly, except for ERβ in cancer cells nuclei, that appeared to be higher after ADT (TSS 6.00 vs. 3.25, p_Mann-Whitney=0.042). Expression of TβRII appeared to be significantly higher for nuclear and lower for membranous staining in ADT cases (Mann-Whitney test, TSS 2.33 vs. 1.20, p=0.002 and 0 vs. 0.58, p<0.001, respectively). Only in ADT cases CD44 was significantly higher in CD133⁺ tumors, and N-cad WSI correlated with CD44 expression, while ERα in both stroma and cancer cells correlated with epithelial AR (r=0.55 and r=0.54, p_Spearman<0,05), though these associations were not seen in cases without ADT. Also moderate direct correlation was seen between nuclear TβRII and E-cad (r=0.52, p_Spearman<0,05). Markers expression in pre-ADT biopsies and their dynamic changes on ADT could not be assessed.

Conclusions

ADT influences TβRII and ERβ expression in cancer cells and also modulates EMT and CSC markers and regulators correlations, that may assume that though ADT alone is not sufficient to induce EMT or CSC phenotypes, it may modulate intra-tissue interactions of signaling cascades and alter cell responses to regulating signals.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

M. Puchinskaya.

Funding

Belarusian Republican Foundation for Fundamental Research, grants No. M14M-143, M19M-123.

Disclosure

M. Puchinskaya: Financial Interests, Personal, Invited Speaker: Roche.