» Articles » PMID: 39569369

Real-time Morphometric Analysis of Targeted Therapy for Neuroblastoma Cells in Monolayer and 3D Hydrogels Using Digital Holographic Microscopy

Overview
Journal iScience
Publisher Cell Press
Date 2024 Nov 21
PMID 39569369
Authors
Affiliations
Soon will be listed here.
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 -amplified SK-N-BE (2) and -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.

References
1.
Langhans S . Three-Dimensional Cell Culture Models in Drug Discovery and Drug Repositioning. Front Pharmacol. 2018; 9:6. PMC: 5787088. DOI: 10.3389/fphar.2018.00006. View

2.
Echavidre W, Picco V, Faraggi M, Montemagno C . Integrin-αvβ3 as a Therapeutic Target in Glioblastoma: Back to the Future?. Pharmaceutics. 2022; 14(5). PMC: 9144720. DOI: 10.3390/pharmaceutics14051053. View

3.
Chen M, Lu C, Sun J, Chen X, Dai J, Cai J . Diagnostic and prognostic value of serum vitronectin levels in human glioma. J Neurol Sci. 2016; 371:54-59. DOI: 10.1016/j.jns.2016.10.022. View

4.
Trigg R, Turner S . ALK in Neuroblastoma: Biological and Therapeutic Implications. Cancers (Basel). 2018; 10(4). PMC: 5923368. DOI: 10.3390/cancers10040113. View

5.
Schvartz I, Seger D, SHALTIEL S . Vitronectin. Int J Biochem Cell Biol. 1999; 31(5):539-44. DOI: 10.1016/s1357-2725(99)00005-9. View