title: A new role for microRNAs, as ligands of Toll-like receptors.
abstract: Tumor microenvironment plays a central role in the development and dissemination of cancer cells. In addition to study each specific cellular component of the microenvironment, it has become clear that it is the type and amount of information that cells exchange that ultimately affects cancer phenotype. Recently, it has been discovered that intercellular communication occurs through the release of microvesicles and exosomes, whose cargo represents the information released by one cell to a recipient cell. A key component of this cargo is represented by microRNAs (miRNAs), small non-coding RNAs with gene regulatory functions. We discovered that miRNAs released by cancer cells within microvesicles can reach and bind to Toll-like receptors (TLRs) in surrounding immune cells, and activate them in a paracrine loop. As a result, immune cells produce cytokines that increase cell proliferation and metastatic potential. This discovery provides the rationale for the development of new drugs that might be used in the treatment of cancer as well as other inflammation-related diseases.
authors.affiliation: Department of Pediatrics and Molecular Microbiology and Immunology, Keck School of Medicine, Norris Comprehensive Cancer Center, Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, University of Southern California, Los Angeles, CA, USA. mfabbri@chla.usc.edu
authors.forename: Muller
authors.initials: M
authors.lastname: Fabbri
authors.forename: Alessio
authors.initials: A
authors.lastname: Paone
authors.forename: Federica
authors.initials: F
authors.lastname: Calore
authors.forename: Roberta
authors.initials: R
authors.lastname: Galli
authors.forename: Carlo M
authors.initials: CM
authors.lastname: Croce
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000276:immunology / Q000378:metabolism; D002450:Cell Communication; D049109:Cell Proliferation; D016207:Cytokines / Q000276:immunology; D055354:Exosomes; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000276:immunology; D008024:Ligands; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism*; D051193:Toll-Like Receptors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014158:Transcription, Genetic; D059016:Tumor Microenvironment
chemical_list: D014408:Biomarkers, Tumor; D016207:Cytokines; D008024:Ligands; D035683:MicroRNAs; D012334:RNA, Neoplasm; D051193:Toll-Like Receptors
keywords: IL-6; TNF-α; Toll-like receptors; exosomes; metastasis; microRNAs; tumor microenvironment