Heme Oxygenase-1 as a potential target in Prostate Cancer

COTIGNOLA JAVIER; VAZQUEZ ELBA S.; ANSELMINO NICOLAS; GUERON GERALDINE

Magdeburg

Simposio; Interdisciplinary Autumn School for Reproductive Sciences and related Research Fields; 2017

Introduction: The prostate is an accessory sexual gland of the male reproductive organ which helps make and store seminal fluid. Prostate Cancer (PCa) is the most frequently diagnosed cancer in men and the second cause of cancer-associated death in men. Cancer, or more often cancer treatments, can interfere with some parts of the reproductive process and affect men ability to have children. Inflammation is one of the main risk factors for this disease. The anti-oxidant protein Heme Oxygenase-1 (HO-1) appears as a potential target in PCa, keeping the cellular homeostasis.Methods: HO-1 immunohistochemical analysis: commercial PCa tissue micro arrays (TMAs) we screened for HO-1 across the different prostate tissues. In vivo: male nude atimic mice were injected s.c. with PC3HO-1 and PC3pcDNA3 cells (3.6×106). Twenty-three days after xenograft generation, tumors were excised and processed.Immunofluorescence: PC3 Cells were treated with hemin (70 μM, 24 h), and immunostained against E-cadherin and β-catenin. Confocal microscopy was carried on to imaged samples.Results: HO-1 positive staining was increased in the pathologic tissue, with the major increment in Chronic Inflammation (67%).We found that HO-1 up-regulation impairs PCa tumor growth and angiogenesis in vivo and down-regulates the expression of target genes associated with inflammation. HO-1 also up-regulate E-cadherin and β-catenin expression, and relocate them to the cell membrane.Conclusions: HO-1 is associated to a less aggressive phenotype in PCa. A better understanding of the molecular mechanism implicated in PCa will allow to find new treatments which improve the quality of the patient's life.