title: Exosomes enriched in stemness/metastatic-related mRNAS promote oncogenic potential in breast cancer.
abstract: Cancer cells efficiently transfer exosome contents (essentially mRNAs and microRNAs) to other cell types, modifying immune responses, cell growth, angiogenesis and metastasis. Here we analyzed the exosomes release by breast tumor cells with different capacities of stemness/metastasis based on CXCR4 expression, and evaluated their capacity to generate oncogenic features in recipient cells. Breast cancer cells overexpressing CXCR4 showed an increase in stemness-related markers, and in proliferation, migration and invasion capacities. Furthermore, recipient cells treated with exosomes from CXCR4-cells showed increased in the same abilities. Moreover, inoculation of CXCR4-cell-derived exosomes in immunocompromised mice stimulated primary tumor growth and metastatic potential. Comparison of nucleic acids contained into exosomes isolated from patients revealed a "stemness and metastatic" signature in exosomes of patients with worse prognosis. Finally, our data supported the view that cancer cells with stem-like properties show concomitant metastatic behavior, and their exosomes stimulate tumor progression and metastasis. Exosomes-derived nucleic acids from plasma of breast cancer patients are suitable markers in the prognosis of such patients.
authors.affiliation: "Mecanismos Moleculares Tumorales" Research Group, Department of Medical Oncology, IDIPHIM, Instituto de Investigación Sanitaria Puerta de Hierro, Madrid, E-28222, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Rodríguez
authors.affiliation: "Mecanismos Moleculares Tumorales" Research Group, Department of Medical Oncology, IDIPHIM, Instituto de Investigación Sanitaria Puerta de Hierro, Madrid, E-28222, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Silva
authors.affiliation: "Señalización Celular en Cáncer" Research Group, Department of Medical Oncology, IDIPHIM, Instituto de Investigación Sanitaria Puerta de Hierro, Madrid, E-28222, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Herrera
authors.affiliation: "Señalización Celular en Cáncer" Research Group, Department of Medical Oncology, IDIPHIM, Instituto de Investigación Sanitaria Puerta de Hierro, Madrid, E-28222, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Herrera
authors.affiliation: "Señalización Celular en Cáncer" Research Group, Department of Medical Oncology, IDIPHIM, Instituto de Investigación Sanitaria Puerta de Hierro, Madrid, E-28222, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Peña
authors.affiliation: Laboratory of Molecular Pathology, Department of Pathology, IDIPHIM, Instituto de Investigación Sanitaria Puerta de Hierro, Madrid, E-28222, Spain.
authors.forename: Paloma
authors.initials: P
authors.lastname: Martín
authors.affiliation: "Señalización Celular en Cáncer" Research Group, Department of Medical Oncology, IDIPHIM, Instituto de Investigación Sanitaria Puerta de Hierro, Madrid, E-28222, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Gil-Calderón
authors.affiliation: Instituto de Investigaciones Biomédicas "Alberto Sols", Department of Cancer Biology, CSIC-UAM, Madrid, E-28029, Spain.
authors.forename: María Jesús
authors.initials: MJ
authors.lastname: Larriba
authors.affiliation: Confocal Microscopy Core Facility, IDIPHIM, Instituto de Investigación Sanitaria Puerta de Hierro, Madrid, E-28222, Spain.
authors.forename: M Josés
authors.initials: MJ
authors.lastname: Coronado
authors.affiliation: Department of Molecular Biology, Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, Centro de Investigación Biomédica en Red de Enfermedades Raras CIBERER-ISCIII, Madrid, E-28049, Spain.|"Diagnóstico y Pronóstico Molecular en Cáncer" Research Group, Department of Medical Oncology, IDIPHIM, Instituto de Investigación Sanitaria Puerta de Hierro, Madrid, E-28222, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Soldevilla
authors.affiliation: Department of Digestive and General Surgery, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, E-28222, Spain.
authors.forename: Víctor S
authors.initials: VS
authors.lastname: Turrión
authors.affiliation: Department of Medical Oncology, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, E-28222, Spain.
authors.forename: Mariano
authors.initials: M
authors.lastname: Provencio
authors.affiliation: Department of Medical Oncology, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, E-28222, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Sánchez
authors.affiliation: Centro de Estudios Biosanitarios, Madrid, E-28029, Spain.
authors.forename: Félix
authors.initials: F
authors.lastname: Bonilla
authors.affiliation: "Mecanismos Moleculares Tumorales" Research Group, Department of Medical Oncology, IDIPHIM, Instituto de Investigación Sanitaria Puerta de Hierro, Madrid, E-28222, Spain.|Molecular Oncology Laboratory, Department of Medical Oncology, IDISSC, Instituto de Investigación Sanitaria San Carlos, Madrid, E28040, Spain.
authors.forename: Vanesa
authors.initials: V
authors.lastname: García-Barberán
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D055354:Exosomes / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: C527276:CXCR4 protein, human; D012333:RNA, Messenger; D019718:Receptors, CXCR4
keywords: breast cancer; exosomes; liquid biopsy; mRNA; stemness and metastasis