Crosstalk Between Heme Oxygenase-1 and the Glycans/Lectins Profile: Immunoregulation in Prostate Cancer

JAWORSKI, FM; GUERON, G; RABINOVICH, GA; VAZQUEZ, ES & LADERACH, DJ

Hannover

Simposio; LISA Summer Academy in Immunology; 2011

LISA Summer Academy in Immunology

Prostate cancer (PCa) is the second leading cause of cancer in men. There are several treatments for PCa as long as it is detected in its early stages. However, there is no effective late-stage PCa treatment and, consequently, establishing molecular patterns that help prevent and control tumor dissemination is crucial for future therapeutic avenues.   Inflammation has been recognized as a risk factor for this disease. Heme Oxygenase-1 (HO-1) is one of the three isoforms of the rate-limiting heme oxygenase enzyme that catabolyzes the degradation of heme into biliverdin with the production of free iron and CO. Several agents involved in oxidative stress, proinflammatory cytokines and diverse anti-inflammatory stimuli alter gene expression and result in an induction of HO-1, which has been linked to decreased cellular proliferation, invasion and migration. Also, there is a growing body of evidence that point toward the capacity of HO-1 to modulate immune reactions. Furthermore, the processes of oncogenesis and metastasis are associated with a dramatic remodeling of cell surface glycans expressed by cancerous, stromal and immune cells in the tumor microenvironment. These alterations result from genetic and epigenetic changes in the activities of glycosiltransferases, glycosidases or chaperones that promote a switch from a “normal” to an “altered” cell surface “glycome”. Galectins, a family of endogenous glycan-binding proteins or lectins, have been shown to be involved in the regulation of many cellular processes, including adhesion, growth, proliferation, differentiation and survival. In addition, galectins can modulate intracellular function and this effect involves direct interactions with distinct signaling pathways. Here we assess the link between these molecules, which could in turn shed light onto the regulatory circuits underlying PCa tumor progression.