Heme oxygenase-1 is involved in prostate cancer cells-bone interaction

FERRANDO MERCEDES; ELGUERO BELEN; MEISS ROBERTO; TZELEPI VASSILIKI ; DE SIERVI ADRIANA; NAVONE NORA; VAZQUEZ ELBA

ORLANDO, FLORIDA

Congreso; American Association for Cancer Research 102nd Annual Meeting 2011; 2011

American Association for Cancer Research (AACR)

Prostate cancer metastasis is well characterized by its tropism to the bone with metastatic lesions being typically osteoblastic. Osteoblasts produce factors that promote growth and survival of prostate cancer cells, but the molecular nature of this interaction is still unknown. Previous reports from our laboratory documented that heme oxygenase-1 (HO-1) is expressed in primary prostate carcinomas and is localized in the nucleus. Recently, the involvement of HO-1 in bone metabolism has been reported. The aim of this study is to investigate the role of HO-1 in the interaction between prostate cancer cells and bone. We analyzed the expression of HO-1 by immunohistochemistry using a tissue microarray generated from 12 castrate-resistant prostate cancer specimens (MDA Anderson Cancer Center), growing as xenografts in male CB17 SCID wild or castrated mice. Each of these tumors led to clinically relevant biological models to study human prostate cancer progression. All samples showed cytoplasmic HO-1 staining of varying intensity. Intense positive nuclear staining was also detected in 3/5 tumors with neuroendocrine morphology. HO-1 expression was correlated with other markers such as PSA, AR and Ki-67 expression. Co- cultures of the osteolytic PC3 cancer cell line with PMO (primary mice osteoblasts) demonstrated that HO-1 induction in PC3 cells abolished the PC3- induced loss of osteoblasts and significantly increased Dickkopf-1 expression in tumor cells. Furthermore, using PC3-PMO co-cultures, we found that HO-1 induction in prostate cancer cells increased mRNA levels of Runx-2 and Cyclin D1 and diminished !-catenin protein expression in PMO. These results clearly indicate the involvement of HO-1 in the interaction between prostate cancer cells and bone. The study of the molecular mechanisms of this interaction will provide effective therapeutic interventions.