title: Microenvironmental control of malignancy exerted by RNASET2, a widely conserved extracellular RNase.
abstract: A recent body of evidence indicates an active role for stromal (mis)-regulation in the progression of neoplasias. Within this conceptual framework, genes belonging to the growing but still poorly characterized class of tumor antagonizing/malignancy suppressor genes (TAG/MSG) seem to play a crucial role in the regulation of the cross-talk between stromal and epithelial cells by controlling malignant growth in vivo without affecting any cancer-related phenotype in vitro. Here, we have functionally characterized the human RNASET2 gene, which encodes the first human member of the widespread Rh/T2/S family of extracellular RNases and was recently found to be down-regulated at the transcript level in several primary ovarian tumors or cell lines and in melanoma cell lines. Although we could not detect any activity for RNASET2 in several functional in vitro assays, a remarkable control of ovarian tumorigenesis could be detected in vivo. Moreover, the control of ovarian tumorigenesis mediated by this unique tumor suppressor gene occurs through modification of the cellular microenvironment and the induction of immunocompetent cells of the monocyte/macrophage lineage. Taken together, the data presented in this work strongly indicate RNASET2 as a previously unexplored member of the growing family of tumor-antagonizing genes.
authors.affiliation: Dipartimento di Biotecnologie e Scienze Molecolari, Faculty of Medicine, Università degli Studi dell'Insubria, 21100 Varese, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Acquati
authors.forename: Sabrina
authors.initials: S
authors.lastname: Bertilaccio
authors.forename: Annalisa
authors.initials: A
authors.lastname: Grimaldi
authors.forename: Laura
authors.initials: L
authors.lastname: Monti
authors.forename: Raffaella
authors.initials: R
authors.lastname: Cinquetti
authors.forename: Paolo
authors.initials: P
authors.lastname: Bonetti
authors.forename: Marta
authors.initials: M
authors.lastname: Lualdi
authors.forename: Laura
authors.initials: L
authors.lastname: Vidalino
authors.forename: Marco
authors.initials: M
authors.lastname: Fabbri
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Sacco
authors.forename: Nico
authors.initials: N
authors.lastname: van Rooijen
authors.forename: Paola
authors.initials: P
authors.lastname: Campomenosi
authors.forename: Davide
authors.initials: D
authors.lastname: Vigetti
authors.forename: Alberto
authors.initials: A
authors.lastname: Passi
authors.forename: Cristina
authors.initials: C
authors.lastname: Riva
authors.forename: Carlo
authors.initials: C
authors.lastname: Capella
authors.forename: Francesca
authors.initials: F
authors.lastname: Sanvito
authors.forename: Claudio
authors.initials: C
authors.lastname: Doglioni
authors.forename: Laura
authors.initials: L
authors.lastname: Gribaldo
authors.forename: Paolo
authors.initials: P
authors.lastname: Macchi
authors.forename: Antonio
authors.initials: A
authors.lastname: Sica
authors.forename: Douglas M
authors.initials: DM
authors.lastname: Noonan
authors.forename: Paolo
authors.initials: P
authors.lastname: Ghia
authors.forename: Roberto
authors.initials: R
authors.lastname: Taramelli
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D066298:In Vitro Techniques; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D012260:Ribonucleases / Q000235:genetics / Q000276:immunology*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000276:immunology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D025521:Tumor Suppressor Proteins; D012260:Ribonucleases; C425232:RNASET2 protein, human