DE SIERVI Adriana
Heme Oxygenase-1 (HO-1) Expression in Prostate Cancer Cells Modulates the Oxidative Response in Bone Cells.
FERRANDO M; WAN X; MEISS R; YANG J; DE SIERVI A; NAVONE N; VAZQUEZ E
PUBLIC LIBRARY SCIENCE
Lugar: San Francisco; Año: 2013 vol. 8 p. 1 - 14
Prostate cancer (PCa) is a leading cause of death among males. It is currently estimated that inflammatoryresponses are linked to 15-20% of all deaths from cancer worldwide. PCa is dominated by complications arising frommetastasis to the bone where the tumor cells interact with the bone microenvironment impairing the balance betweenbone formation and degradation. However, the molecular nature of this interaction is not completely understood.Heme oxygenase-1 (HO-1) counteracts oxidative damage and inflammation. Previous studies from our laboratoryshowed that HO-1 is implicated in PCa, demonstrating that endogenous HO-1 inhibits bone derived-prostate cancercells proliferation, invasion and migration and decreases tumor growth and angiogenesis in vivo. The aim of this workwas to analyze the impact of HO-1 modulated PCa cells on osteoblasts proliferation in vitro and on bone remodelingin vivo. Using a co-culture system of PC3 cells with primary mice osteoblasts (PMOs), we demonstrated that HO-1pharmacological induction (hemin treatment) abrogated the diminution of PMOs proliferation induced by PCa cellsand decreased the expression of osteoclast-modulating factors in osteoblasts. No changes were detected in theexpression of genes involved in osteoblasts differentiation. However, co-culture of hemin pre-treated PC3 cells (PC3Hem) with PMOs provoked an oxidative status and activated FoxO signaling in osteoblasts. The percentage of activeosteoblasts positive for HO-1 increased in calvarias explants co-cultured with PC3 Hem cells. Nuclear HO-1expression was detected in tumors generated by in vivo bone injection of HO-1 stable transfected PC3 (PC3HO-1)cells in the femur of SCID mice. These results suggest that HO-1 has the potential to modify the bonemicroenvironment impacting on PCa bone metastasis.