Microenvironmental control of malignancy exerted by RNASET2, a widely conserved extracellular RNase

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 mammalian member of the widespread Rh/T2/S family of extracellular RNases and was recently found to be downregulated 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 new 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 new member of the growing family of tumor-antagonizing genes.

ACQUATI Francesco;  BERTILACCIO Sabrina;  GRIMALDI Annalisa;  MONTI Laura;  CINQUETTI Raffaella;  BONETTI Paolo;  LUALDI Marta;  VIDALINO Laura;  FABBRI Marco;  SACCO Maria-Grazia;  VAN ROOIJEN Nico;  CAMPOMENOSI Paola;  VIGETTI Davide;  PASSI Alberto;  RIVA Cristina;  CAPELLA Carlo;  SANVITO Francesca;  DOGLIONI Claudio;  GRIBALDO Laura;  MACCHI Paolo;  SICA Antonio;  NOONAN Douglas;  GHIA Paolo;  TARAMELLI Roberto; 

2011-01-20

NATL ACAD SCIENCES

JRC62237

0027-8424,   

https://publications.jrc.ec.europa.eu/repository/handle/JRC62237,   

10.1073/pnas.1013746108,