Crosstalk between Hemo Oxygenase-1 and the glycan/lectin profile in prostate Cancer

JAWORSKI FELIPE MARTIN, GUERON GERALDINE, COMPAGNO DANIEL, RABINOVICH GABRIEL, LADERACH DIEGO JOSÉ AND VAZQUEZ ELBA SUSANA

Edinburgo

Congreso; 7th International Congress on Heme Oxygenases and Related Enzymes; 2012

Prostate cancer (PCa) is the second leading cause of cancer in men. Although there are several treatments for PCa in its early stages, there are no effective late-stage therapeutic strategies. Therefore, establishing molecular patterns that help prevent and control tumour dissemination is crucial for future clinical approaches. High expression levels of Heme Oxygenase-1 (HO-1), which is induced as a protective mechanism to counteract inflammation, has been associated to hindered PCa growth. Furthermore, malignant transformation involves dramatic remodeling of cell surface glycans and alterations of lectin expression profiles. In this study we assessed a potential crosstalk between HO-1 and the galectin profile in PCa. Using RTqPCR and IHC analysis, we found that subcutaneous tumours that overexpress HO-1 in nu/nu mice showed a significant induction of galectin-1 and galectin-8 compared to control tumours with basal expression of HO-1. However, there was no change in galectin mRNA levels when PCa cell lines were treated with hemin. Likely, the tumour microenvironment could account for the differences observed between the in vitro and in vivo approaches. Taking into account our results and the immunomodulatory properties associated to galectins, we assessed the effect of HO-1 on lymphocyte proliferation. Strikingly, upon HO-1 induction by hemin treatment and stimulation with concavanalin A or áCD3 antibody, both CD8+ and CD4+ T cells displayed enhanced proliferation. These findings imply a connection between HO-1 and galectins, and constitute the start point of a detailed study of the role of galectins in HO-1 immunomodulation in the context of the tumour microenvironment.