Pleiotropic modes of action in tumor cells of RNASET2, an evolutionary highly conserved extracellular RNase

// Marta Lualdi 1 , Edoardo Pedrini 1 , Katia Rea 2 , Laura Monti 1 , Debora Scaldaferri 1 , Marzia Gariboldi 3 , Annalisa Camporeale 4,6 , Paolo Ghia 4,5 , Elena Monti 3 , Antonella Tomassetti 2 , Francesco Acquati 1 and Roberto Taramelli 1 1 Department of Theoretical and Applied Sciences, Università degli Studi dell’Insubria, Varese, Italy 2 Unit of Molecular Therapies, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy 3 Department of Theoretical and Applied Sciences, Università degli Studi dell’Insubria, Busto Arsizio, Italy 4 Division of Molecular Oncology and Department of Onco-Hematology, IRCCS Ospedale San Raffaele, Milan, Italy 5 Università Vita-Salute San Raffaele, Milan, Italy 6 Present address: Molecular Biotechnology Center and Department of Molecular Biotechnology and Life Sciences, University of Turin, Turin, Italy Correspondence to: Francesco Acquati, email: // Keywords : RNase, Ovarian cancer, Microenvironment, Stress response Received : December 01, 2014 Accepted : February 02, 2015 Published : March 08, 2015 Abstract As widely recognized, tumor growth entails a close and complex cross-talk among cancer cells and the surrounding tumor microenvironment. We recently described the human RNASET2 gene as one key player of such microenvironmental cross-talk. Indeed, the protein encoded by this gene is an extracellular RNase which is able to control cancer growth in a non-cell autonomous mode by inducing a sustained recruitment of immune-competent cells belonging to the monocyte/macrophage lineage within a growing tumor mass. Here, we asked whether this oncosuppressor gene is sensitive to stress challenges and whether it can trigger cell-intrinsic processes as well. Indeed, RNASET2 expression levels were consistently found to increase following stress induction. Moreover, changes in RNASET2 expression levels turned out to affect several cancer-related parameters in vitro in an ovarian cancer cell line model. Of note, a remarkable rearrangement of the actin cytoskeleton organization, together with changes in cell adhesion and motility, emerged as putative mechanisms by which such cell-autonomous role could occur. Altogether, these biological features allow to put forward the hypothesis that the RNASET2 protein can act as a molecular barrier for limiting the damages and tissue remodeling events occurring during the earlier step of cell transformation.