title: Pleiotropic modes of action in tumor cells of RNASET2, an evolutionary highly conserved extracellular RNase.
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.
authors: Department of Theoretical and Applied Sciences, Università degli Studi dell'Insubria, Varese, Italy.
authors: Marta
authors: M
authors: Lualdi
authors: Department of Theoretical and Applied Sciences, Università degli Studi dell'Insubria, Varese, Italy.
authors: Edoardo
authors: E
authors: Pedrini
authors: Unit of Molecular Therapies, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors: Katia
authors: K
authors: Rea
authors: Department of Theoretical and Applied Sciences, Università degli Studi dell'Insubria, Varese, Italy.
authors: Laura
authors: L
authors: Monti
authors: Department of Theoretical and Applied Sciences, Università degli Studi dell'Insubria, Varese, Italy.
authors: Debora
authors: D
authors: Scaldaferri
authors: Department of Theoretical and Applied Sciences, Università degli Studi dell'Insubria, Busto Arsizio, Italy.
authors: Marzia
authors: M
authors: Gariboldi
authors: Division of Molecular Oncology and Department of Onco-Hematology, IRCCS Ospedale San Raffaele, Milan, Italy.|Present address: Molecular Biotechnology Center and Department of Molecular Biotechnology and Life Sciences, University of Turin, Turin, Italy.
authors: Annalisa
authors: A
authors: Camporeale
authors: Division of Molecular Oncology and Department of Onco-Hematology, IRCCS Ospedale San Raffaele, Milan, Italy.|Università Vita-Salute San Raffaele, Milan, Italy.
authors: Paolo
authors: P
authors: Ghia
authors: Department of Theoretical and Applied Sciences, Università degli Studi dell'Insubria, Busto Arsizio, Italy.
authors: Elena
authors: E
authors: Monti
authors: Unit of Molecular Therapies, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors: Antonella
authors: A
authors: Tomassetti
authors: Department of Theoretical and Applied Sciences, Università degli Studi dell'Insubria, Varese, Italy.
authors: Francesco
authors: F
authors: Acquati
authors: Department of Theoretical and Applied Sciences, Università degli Studi dell'Insubria, Varese, Italy.
authors: Roberto
authors: R
authors: Taramelli
mesh_terms: D000818:Animals; D048708:Cell Growth Processes / Q000502:physiology; D015687:Cell Hypoxia / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D005260:Female; D006367:HeLa Cells; D064593:Heterografts; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012260:Ribonucleases / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D059016:Tumor Microenvironment; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism
chemical_list: D025521:Tumor Suppressor Proteins; D012260:Ribonucleases; C425232:RNASET2 protein, human
keywords: RNase; microenvironment; ovarian cancer; stress response