HO-1 Interactors Involved in the Colonization of the Bone Niche: Role of ANXA2 in Prostate Cancer Progression

ANSELMINO, NICOLAS; LAGE VICKERS, SOFÍA; PAEZ, ALEJANDRA; NAVONE, NORA; GUERON, GERALDINE; BIZZOTTO, JUAN ANTONIO; ORTIZ, EMILIANO GERMAN; LABANCA, ESTEFANÍA; COTIGNOLA, JAVIER; SANCHIS, PABLO ANTONIO; VALACCO, PÍA; MEISS, ROBERTO; VAZQUEZ, ELBA SUSANA

Biomolecules

MDPI

Año: 2020

2218-273X

Abstract: Background: Prostate cancer (PCa) dissemination shows a tendency to develop in thebone, where heme oxygenase 1 (HO-1) plays a critical role in bone remodeling. Previously byLC/ESI-MSMS, we screened for HO-1 interacting proteins and identified annexin 2 (ANXA2). Theaim of this study was to analyze the relevance of ANXA2/HO-1 in PCa and bone metastasis.Methods: We assessed ANXA2 levels using a co-culture transwell system of PC3 cells (pre-treatedor not with hemin, an HO-1 specific inducer) and the pre-osteoclastic Raw264.7 cell line. Results:Under co-culture conditions, ANXA2 mRNA levels were significantly modulated in both cell lines.Immunofluorescence analysis unveiled a clear ANXA2 reduction in cell membrane immunostainingfor Raw264.7 under the same conditions. This effect was supported by the detection of a decreasein Ca2+ concentration in the conditioned medium. HO-1 induction in tumor cells prevented both,the ANXA2 intracellular relocation and the decrease in Ca2+ concentration. Further, secretomeanalysis revealed urokinase (uPA) as a key player in the communication between osteoclastprogenitors and PC3 cells. To assess the clinical significance of ANXA2/HO-1, we performed abioinformatics analysis and identified that low expression of each gene strongly associated withpoor prognosis in PCa regardless of the clinico-pathological parameters assessed. Further, thesegenes appear to behave in a dependent manner. Conclusions: ANXA2/HO-1 rises as a critical axisin PCa.