title: Cancer-associated fibroblasts release exosomal microRNAs that dictate an aggressive phenotype in breast cancer.
abstract: Cancer-associated fibroblasts (CAFs) are the major components of the tumor microenvironment. They may drive tumor progression, although the mechanisms involved are still poorly understood. Exosomes have emerged as important mediators of intercellular communication in cancer. They mediate horizontal transfer of microRNAs (miRs), mRNAs and proteins, thus affecting breast cancer progression. Differential expression profile analysis identified three miRs (miRs -21, -378e, and -143) increased in exosomes from CAFs as compared from normal fibroblasts. Immunofluorescence indicated that exosomes may be transferred from CAFs to breast cancer cells, releasing their cargo miRs. Breast cancer cells (BT549, MDA-MB-231, and T47D lines) exposed to CAF exosomes or transfected with those miRs exhibited a significant increased capacity to form mammospheres, increased stem cell and epithelial-mesenchymal transition (EMT) markers, and anchorage-independent cell growth. These effects were reverted by transfection with anti-miRs. Similarly to CAF exosomes, normal fibroblast exosomes transfected with miRs -21, -378e, and -143 promoted the stemness and EMT phenotype of breast cancer cells. Thus, we provided evidence for the first time of the role of CAF exosomes and their miRs in the induction of the stemness and EMT phenotype in different breast cancer cell lines. Indeed, CAFs strongly promote the development of an aggressive breast cancer cell phenotype.
authors.affiliation: IRCCS-SDN, Naples, Italy.
authors.forename: Elvira
authors.initials: E
authors.lastname: Donnarumma
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology, "Federico II" University of Naples, Naples, Italy.
authors.forename: Danilo
authors.initials: D
authors.lastname: Fiore
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology, "Federico II" University of Naples, Naples, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Nappa
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology, "Federico II" University of Naples, Naples, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Roscigno
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology, "Federico II" University of Naples, Naples, Italy.
authors.forename: Assunta
authors.initials: A
authors.lastname: Adamo
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology, "Federico II" University of Naples, Naples, Italy.
authors.forename: Margherita
authors.initials: M
authors.lastname: Iaboni
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology, "Federico II" University of Naples, Naples, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Russo
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology, "Federico II" University of Naples, Naples, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Affinito
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology, "Federico II" University of Naples, Naples, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Puoti
authors.affiliation: University Hospital Basel, Basel, Switzerland.
authors.forename: Cristina
authors.initials: C
authors.lastname: Quintavalle
authors.affiliation: IEOS, CNR, Naples, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Rienzo
authors.affiliation: University Hospital Basel, Basel, Switzerland.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Piscuoglio
authors.affiliation: Department of Surgical and Oncology, Clinica Mediterranea, Naples, Italy.
authors.forename: Renato
authors.initials: R
authors.lastname: Thomas
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology, "Federico II" University of Naples, Naples, Italy.|IEOS, CNR, Naples, Italy.
authors.forename: Gerolama
authors.initials: G
authors.lastname: Condorelli
mesh_terms: D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D000072645:Cancer-Associated Fibroblasts; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition; D055354:Exosomes / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009367:Neoplasm Staging; D010641:Phenotype; D011379:Prognosis; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D059016:Tumor Microenvironment / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C542359:MIRN143 microRNA, human; C524940:MIRN21 microRNA, human; C526012:MIRN378 microRNA, human; D035683:MicroRNAs
keywords: breast cancer; cancer-associated fibroblasts; exosomes; microRNAs; microenvironment