Unraveling the extracellular matrix-tumor cell interactions to aid better targeted therapies for neuroblastoma.

Fecha de publicación: 25/10/2021 Fecha Ahead of Print: 28/08/2021

Autores de INCLIVA

Participantes ajenos a INCLIVA

Burgos-Panadero, Rebeca
El Moukhtari, Souhaila H
Noguera, Inmaculada
Rodriguez-Nogales, Carlos
Vicente-Munuera, Pablo
Canete, Adela
Blanco-Prieto, Maria J

Grupos y Plataformas de I+D+i

Grupo de investigación en Enfermedades Metabólicas

Established Researcher

Herminia González Navarro
Grupo de Investigación Translacional de Tumores Sólidos Pediátricos

Leading Researcher

Samuel Navarro Fos

Abstract

Treatment in children with high-risk neuroblastoma remains largely unsuccessful due to the development of metastases and drug resistance. The biological complexity of these tumors and their microenvironment represent one of the many challenges to face. Matrix glycoproteins such as vitronectin act as bridge elements between extracellular matrix and tumor cells and can promote tumor cell spreading. In this study, we established through a clinical cohort and preclinical models that the interaction of vitronectin and its ligands, such as a(v) integrins, are related to the stiffness of the extracellular matrix in high-risk neuroblastoma. These marked alterations found in the matrix led us to specifically target tumor cells within these altered matrices by employing nanomedicine and combination therapy. Loading the conventional cytotoxic drug etoposide into nanoparticles significantly increased its efficacy in neuroblastoma cells. We noted high synergy between etoposide and cilengitide, a high-affinity cyclic pentapeptide a(v) integrin antagonist. The results of this study highlight the need to characterize cell-extracellular matrix interactions, to improve patient care in high-risk neuroblastoma.

Datos de la publicación

ISSN/ISSNe:: 0378-5173, 1873-3476
Tipo:: Article
Páginas:: 121058-121058
DOI:: 10.1016/j.ijpharm.2021.121058
PubMed:: 34461172

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Métricas

Filiaciones

Burgos-Panadero, Rebeca:: CIBER. Department of Pathology, Medical School, University of Valencia - INCLIVA Biomedical Health Research Institute, 46010 Valencia, Spain. Low Prevalence Tumors, Centro de investigación biomédica en red de cáncer (CIBERONC), Instituto de Salud Carlos III, 28029 Madrid, Spain

Instituto de Investigación. Department of Pathology, Medical School, University of Valencia - INCLIVA Biomedical Health Research Institute, 46010 Valencia, Spain. Low Prevalence Tumors, Centro de investigación biomédica en red de cáncer (CIBERONC), Instituto de Salud Carlos III, 28029 Madrid, Spain
El Moukhtari, Souhaila H:: Department of Pharmaceutical Technology and Chemistry, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain; Instituto de Investigación Sanitaria de Navarra (IdiSNA), 31008 Pamplona, Spain
Noguera, Inmaculada:: Universidad. Central Support Service for Experimental Research (SCSIE), University of Valencia, Burjassot, Valencia, Spain
Rodriguez-Nogales, Carlos:: Department of Pharmaceutical Technology and Chemistry, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain; Instituto de Investigación Sanitaria de Navarra (IdiSNA), 31008 Pamplona, Spain
Martin-Vano, Susana:: CIBER. Department of Pathology, Medical School, University of Valencia - INCLIVA Biomedical Health Research Institute, 46010 Valencia, Spain. Low Prevalence Tumors, Centro de investigación biomédica en red de cáncer (CIBERONC), Instituto de Salud Carlos III, 28029 Madrid, Spain

Instituto de Investigación. Department of Pathology, Medical School, University of Valencia - INCLIVA Biomedical Health Research Institute, 46010 Valencia, Spain. Low Prevalence Tumors, Centro de investigación biomédica en red de cáncer (CIBERONC), Instituto de Salud Carlos III, 28029 Madrid, Spain
Vicente-Munuera, Pablo:: Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla and Departamento de Biología Celular, Universidad de Sevilla, Seville 41013, Spain
Canete, Adela:: Pediatric Oncology, La Fe Hospital, Av. Fernando Abril Martorell 106, 46026 Valencia, Spain
Navarro, Samuel:: CIBER. Department of Pathology, Medical School, University of Valencia - INCLIVA Biomedical Health Research Institute, 46010 Valencia, Spain. Low Prevalence Tumors, Centro de investigación biomédica en red de cáncer (CIBERONC), Instituto de Salud Carlos III, 28029 Madrid, Spain

Instituto de Investigación. Department of Pathology, Medical School, University of Valencia - INCLIVA Biomedical Health Research Institute, 46010 Valencia, Spain. Low Prevalence Tumors, Centro de investigación biomédica en red de cáncer (CIBERONC), Instituto de Salud Carlos III, 28029 Madrid, Spain
Blanco-Prieto, Maria J:: Department of Pharmaceutical Technology and Chemistry, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain; Instituto de Investigación Sanitaria de Navarra (IdiSNA), 31008 Pamplona, Spain
Noguera, Rosa:: CIBER. Department of Pathology, Medical School, University of Valencia - INCLIVA Biomedical Health Research Institute, 46010 Valencia, Spain. Low Prevalence Tumors, Centro de investigación biomédica en red de cáncer (CIBERONC), Instituto de Salud Carlos III, 28029 Madrid, Spain

Instituto de Investigación. Department of Pathology, Medical School, University of Valencia - INCLIVA Biomedical Health Research Institute, 46010 Valencia, Spain. Low Prevalence Tumors, Centro de investigación biomédica en red de cáncer (CIBERONC), Instituto de Salud Carlos III, 28029 Madrid, Spain