Real-time morphometric analysis of targeted therapy for neuroblastoma cells in monolayer and 3D hydrogels using digital holographic microscopy.

Autores de INCLIVA

• 

  Sofía Granados Aparici

  Autor

• 

  Isaac Vieco Martí

  Autor

• 

  María Amparo López Carrasco

  Autor

• 

  Samuel Navarro Fos

  Autor

• 

  Rosa Noguera Salva

  Autor

Grupos y Plataformas de I+D+i

• Grupo de Investigación Translacional de Tumores Sólidos Pediátricos

  

  Leading Researcher

  Samuel Navarro Fos

Abstract

High-risk neuroblastoma (HR-NB) patient treatment is currently insufficient and challenging due to its high clinical, morphological, and genetic heterogeneity as well as the scarcity of available samples for research. We used a gelatin- and silk fibroin-based hydrogel system with cross-linked vitronectin (VN) as an artificial biomimetic three-dimensional (3D) environment to mirror aggressive neuroblastoma (NB) tumors and tested long-term cell response to Cilengitide (CLG). Based on our previous studies and others using the integrin inhibitor CLG as a potential mechanotherapy drug, we show that CLG caused cell detachment in monolayer cultures of MYCN-amplified SK-N-BE (2) and ALK-mutated SH-SY5Y human neuroblastoma cell lines. Cell detachment and aggregation were maintained in hydrogel-free monolayer cells whereas cells embedded in hydrogels presented different responses to treatment, suggesting differential anoikis resistance between the two cell lines. This underscores the advantages of testing therapeutic approaches using real-time imaging of tumor cells in 3D biomimetic models and its contribution to precision medicine.

© 2024 The Authors.

Keywords

• Cancer; Cell biology; Mechanobiology; Methodology in biological sciences