Research Papers:
Exosomes enriched in stemness/metastatic-related mRNAS promote oncogenic potential in breast cancer
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Abstract
Marta Rodríguez1, Javier Silva1, Alberto Herrera2, Mercedes Herrera2, Cristina Peña2, Paloma Martín3, Beatriz Gil-Calderón2, María Jesús Larriba4, Mª José Coronado5, Beatriz Soldevilla6,7, Víctor S. Turrión8, Mariano Provencio9, Antonio Sánchez9, Félix Bonilla10, Vanesa García-Barberán1,11
1“Mecanismos Moleculares Tumorales” Research Group, Department of Medical Oncology, IDIPHIM, Instituto de Investigación Sanitaria Puerta de Hierro, Madrid, E-28222, Spain
2“Señalización Celular en Cáncer” Research Group, Department of Medical Oncology, IDIPHIM, Instituto de Investigación Sanitaria Puerta de Hierro, Madrid, E-28222, Spain
3Laboratory of Molecular Pathology, Department of Pathology, IDIPHIM, Instituto de Investigación Sanitaria Puerta de Hierro, Madrid, E-28222, Spain
4Instituto de Investigaciones Biomédicas “Alberto Sols”, Department of Cancer Biology, CSIC-UAM, Madrid, E-28029, Spain
5Confocal Microscopy Core Facility, IDIPHIM, Instituto de Investigación Sanitaria Puerta de Hierro, Madrid, E-28222, Spain
6Department 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
7“Diagnóstico y pronóstico molecular en cáncer” Research Group, Department of Medical Oncology, IDIPHIM, Instituto de Investigación Sanitaria Puerta de Hierro, Madrid, E-28222, Spain
8Department of Digestive and General Surgery, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, E-28222, Spain
9Department of Medical Oncology, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, E-28222, Spain
10Centro de Estudios Biosanitarios, Madrid, E-28029, Spain
11Molecular Oncology Laboratory, Department of Medical Oncology, IDISSC, Instituto de Investigación Sanitaria San Carlos, Madrid, E28040, Spain
Correspondence to:
Félix Bonilla, e-mail: [email protected]
Vanesa García-Barberán, e-mail: [email protected]
Keywords: exosomes, liquid biopsy, breast cancer, mRNA, stemness and metastasis
Received: April 22, 2015 Accepted: September 22, 2015 Published: October 26, 2015
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.
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