title: Endothelial exosomes contribute to the antitumor response during breast cancer neoadjuvant chemotherapy via microRNA transfer.
abstract: The interaction between tumor cells and their microenvironment is an essential aspect of tumor development. Therefore, understanding how this microenvironment communicates with tumor cells is crucial for the development of new anti-cancer therapies. MicroRNAs (miRNAs) are small non-coding RNAs that inhibit gene expression. They are secreted into the extracellular medium in vesicles called exosomes, which allow communication between cells via the transfer of their cargo. Consequently, we hypothesized that circulating endothelial miRNAs could be transferred to tumor cells and modify their phenotype. Using exogenous miRNA, we demonstrated that endothelial cells can transfer miRNA to tumor cells via exosomes. Using miRNA profiling, we identified miR-503, which exhibited downregulated levels in exosomes released from endothelial cells cultured under tumoral conditions. The modulation of miR-503 in breast cancer cells altered their proliferative and invasive capacities. We then identified two targets of miR-503, CCND2 and CCND3. Moreover, we measured increased plasmatic miR-503 in breast cancer patients after neoadjuvant chemotherapy, which could be partly due to increased miRNA secretion by endothelial cells. Taken together, our data are the first to reveal the involvement of the endothelium in the modulation of tumor development via the secretion of circulating miR-503 in response to chemotherapy treatment.
authors: Laboratory of Molecular Angiogenesis, GIGA-R, University of Liège, Belgium.
authors: Nicolas
authors: N
authors: Bovy
authors: Laboratory of Molecular Angiogenesis, GIGA-R, University of Liège, Belgium.
authors: Benoît
authors: B
authors: Blomme
authors: Laboratory of Human Genetics, GIGA-R, University of Liège, Belgium.
authors: Pierre
authors: P
authors: Frères
authors: Laboratory of Molecular Angiogenesis, GIGA-R, University of Liège, Belgium.
authors: Stella
authors: S
authors: Dederen
authors: Laboratory of Molecular Angiogenesis, GIGA-R, University of Liège, Belgium.
authors: Olivier
authors: O
authors: Nivelles
authors: Laboratory of Molecular Angiogenesis, GIGA-R, University of Liège, Belgium.
authors: Michelle
authors: M
authors: Lion
authors: Laboratory of Tumor & Development Biology, GIGA-R, University of Liège, Belgium.
authors: Oriane
authors: O
authors: Carnet
authors: Laboratory of Molecular Angiogenesis, GIGA-R, University of Liège, Belgium.
authors: Joseph A
authors: JA
authors: Martial
authors: Laboratory of Tumor & Development Biology, GIGA-R, University of Liège, Belgium.
authors: Agnès
authors: A
authors: Noël
authors: Laboratory of Cell and Tissues Biology, University of Liège, Belgium.
authors: Marc
authors: M
authors: Thiry
authors: Department of Medical Oncology, CHU, Liège, Belgium.
authors: Guy
authors: G
authors: Jérusalem
authors: Laboratory of Human Genetics, GIGA-R, University of Liège, Belgium.
authors: Claire
authors: C
authors: Josse
authors: Laboratory of Human Genetics, GIGA-R, University of Liège, Belgium.
authors: Vincent
authors: V
authors: Bours
authors: Laboratory of Molecular Angiogenesis, GIGA-R, University of Liège, Belgium.
authors: Sébastien P
authors: SP
authors: Tabruyn
authors: Laboratory of Molecular Angiogenesis, GIGA-R, University of Liège, Belgium.
authors: Ingrid
authors: I
authors: Struman
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D017024:Chemotherapy, Adjuvant; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D055354:Exosomes / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D035683:MicroRNAs / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism*; D020360:Neoadjuvant Therapy
chemical_list: D035683:MicroRNAs
keywords: angiogenesis; cancer; exosomes; miR-503; microRNAs