IQUIBICEN   23947
INSTITUTO DE QUIMICA BIOLOGICA DE LA FACULTAD DE CIENCIAS EXACTAS Y NATURALES
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
HEME OXYGENASE 1 (HO-1) MODULATION OF METASTASIS AND STEMNESS PROCESSES IN PROSTATE CANCER
Autor/es:
AYELEN TORO; JAVIER COTIGNOLA; SOFIA LAGE-VICKERS; PABLO SANCHIS; GERALDINE GUERON; AGUSTINA SABATER; ELBA VAZQUEZ; JUAN BIZZOTTO
Lugar:
Buenos Aires (Virtual)
Reunión:
Congreso; LIX Reunión Anual de la Sociedad Argentina de Investigación Clínica; 2021
Resumen:
Within prostate cancer (PCa) tumors, there is a sub-population of cancer stem cells (CSCs) thatenhances the tumor?s capacity to proliferate and metastasize. Thus, stemness represents atherapeutic challenge in PCa. Heme oxygenase 1 (HO-1), the rate-limiting enzyme in hemedegradation, is an essential player in cellular responses to pro-oxidative and pro-inflammatoryinsults. We have reported HO-1 strong anti-tumoral effect in vivo and in vitro, but its associationwith metastasis-stemness (M-S) is still poorly elucidated. In this work, we aimed at describingthe effects of HO-1 overexpression on M-S processes in PCa. Clonogenic assays were performedto evaluate the effect of HO-1 induction on the stem properties of PCa cells. Results showed asignificant reduction in colony formation after HO-1 pharmacological induction with hemin.RNA-Seq analysis was performed to assess differential gene expression of 144 M-S associatedgenes in PC3 hemin vs. PC3 control. We found a significant modulation of 32 markers related tothese processes under HO-1 induction. We assessed the clinical significance of these genesthrough integrative bioinformatics analyses using public data repositories. The Oncominedatabase showed that 15/32 significantly HO-1-modulated genes were differentially expressedin prostate adenocarcinoma vs. normal prostate gland. Hemin treatment reverted theexpression profile observed in PCa tumors. The TCGA-PRAD dataset revealed that ADAM15,BCL2L1, LTBR, MBNL2 and SPINT1 showed the same expression profile as Oncomine. Moreover,PCa patients with high MBNL2 expression showed a significant increase in the diseaseprogression free interval, which is interesting as it is upregulated in PC3 overexpressing HO-1.This was validated by RT-qPCR. This study may cast a new light on PCa treatment, highlighting amultifaceted role for HO-1 in altering these processes by modulating cell plasticity, thussupporting it as a potential therapeutic target for the disease.