CONICET | Buscador de Institutos y Recursos Humanos

Prostate cancer (PCa) is the second leading cause of cancer-associated death in men. Localized PCa can be cured in most cases, but when the disease escapes the confines of the gland, the prospects for cure decrease drastically. Androgen ablation is the most effective way of halting PCa progression, but given sufficient time, growth of the cancer resumes in most cases, and the disease becomes ?castrate resistant?. Bone is the most common and frequently the only site of PCa progression, and men with PCa display characteristically osteoblastic bone metastases, which are the main cause of morbidity and mortality of the disease. Upon metastases, tumoral cells interact with the bone microenvironment interrupting the osteoblastogenesis/osteoclastogenesis tissue balance. Inflammation is one of the main risk factors of this disease. In this context heme oxigenase 1 (HO-1) appears as a potential target in PCa mantaining the cellular homeostasis and counteracting the oxidative and inflammatory damage. We previously showed that HO-1 has tumor suppressor properties in PCa and its induction modulates the effect of tumoral cells on osteoblastic proliferation. The aim of this work was to evaluate HO-1 function in the interaction between the PCa cell and the bone progenitor cell. We used a co-culture system of PC3 cells (derived from human PCa) with MC3T3 cells (murine osteoblast precursors) or PC3 with RAW 264.7 cells (murine osteoclast precursors) in which both cell lines share the medium but are not in physical contact. The PC3 cells where pre-treated or not with hemin (HO-1 inductor, 50µM, 24h) before the co-culture. Using RT-qPCR we evaluated the effect of co-culture and HO-1 on the expression of genes implicated in bone remodeling. The expression levels of DKK1, FOXO3 and PTHrP were modified (P