IQUIBICEN   23947
INSTITUTO DE QUIMICA BIOLOGICA DE LA FACULTAD DE CIENCIAS EXACTAS Y NATURALES
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
CLINICAL RELEVANCE OF ANNEXIN 2 IN PROS- TATE CANCER BONE METASTASIS AND ITS ASSOCIATION WITH HEME-OXYGENASE 1
Autor/es:
ANSELMINO NICOLAS; DAIANA LEONARDI; ORTIZ EMILIANO GERMAN; GERALDINE GUERON; ELBA VAZQUEZ; ALEJANDRA PAEZ; COTIGNOLA JAVIER
Lugar:
Mar del Plata
Reunión:
Congreso; Sociedad argentina de investigacion clinica; 2016
Resumen:
HO-1 is a critical mediator of cellular homeostasis. In prostate cancer (PCa), HO-1 may have a regulatory role beyond its enzymatic activity. We screened for HO1 interacting proteins using a proteomics approach. PC3 cells Were transiently transfected with FL AGHO-1 , treated With H202 and the immunoprecipitated protein complexes were subjected to LC ESI MS/ MS. Proteomics analysis revealed the presence of annexin A2 (ANXA2) among HO1 interacting proteins. Interestingly ANXA2 was significantly downregulated across the Oncomine database in prostate adenocarcinoma vs. normal prostate gland, lying Within the 13 lowest ranked genes, with a p-value of 0.003 . We also screened for HO-1 and ANXA expression in PCa tissue micro arrays (TMAs) . When assessing HO-1 across the different TNM staging system, the rate of positive cases was higher in T2 T3 N0M0, compared to T2T3 with spreading to regional lymph nodes or the presence of distant metastasis. A reduction in ANXA positive staining as detected bet een normal prostate and adenocarcinoma. Given that bone is the most common homing organ in Ca metastasis, e assessed A A expression levels using a co culture transwell system of PC3 and the pre osteoclastic cell line RAW264.7. When cells were co cultured, ANXA2 mRNA levels were detected significantly upregulated in PC3 cells and diminished in RAW 264.7 . Immunofluorescence analysis has shown there was a clear re-localization of ANXA2 in RAW264.7 towards the cell cytosolic compartment under co culture conditions, with a concomitant reduction in cell membrane immunostaining. Interestingly, hemin pre treatment of tumoral cells prevented these effects. Given the tight association between ANXA2 and cell adhesiveness, HO-1 induction in PCa cells may force bone cells to keep ANXA2 in the cell membrane, preventing the attachment of tumoral cells to the bone niche, impairing bone metastasis.