Pleiotropic modes of action in tumor cells of RNASET2, an evolutionary highly conserved extracellular RNase
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Marta Lualdi1, Edoardo Pedrini1, Katia Rea2, Laura Monti1, Debora Scaldaferri1, Marzia Gariboldi3, Annalisa Camporeale4,6, Paolo Ghia4,5, Elena Monti3, Antonella Tomassetti2, Francesco Acquati1 and Roberto Taramelli1
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
Francesco Acquati, email:
Keywords: RNase, Ovarian cancer, Microenvironment, Stress response
Received: December 01, 2014 Accepted: February 02, 2015 Published: March 08, 2015
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.
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