The pleiotropic roles of the human RNASET2 tumor suppressor gene

The RNASET2 gene encodes for a highly conserved extracellular ribonuclease which has recently been shown to carry out a marked oncosuppressive role by means of modification of the tumor microenvironment. In particular, focusing on two independent ovarian cancer cell models, we recently reported that RNASET2-mediated tumor suppression in vivo involves the recruitment toward the tumor mass of cancer-suppressive innate immune cells belonging to the monocyte/macrophage lineage. Given these premises, we extended our experiments to analyze the effect of RNASET2 on the polarization of human macrophages in vitro. Furthermore, since all previous in vivo experiments have been conducted using nude mice, we started developing a syngeneic mouse model in order to study the role of this gene in an immunocompetent model. Finally, we recently demonstrated that RNASET2 also behaves as a stress response gene and strongly affects the actin cytoskeleton. This prompted us to postulate a role for RNASET2 as a “moonlighting” protein. To shed more lights on its pleiotropic functions, we also started to investigate the role of this gene in the context of mammary tumorigenesis and morphogenesis.