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Cancer Cell International
Published in: Cancer Cell International 1/2022

Open Access 01-12-2022 | Research

Extracellular matrix stiffness mediates radiosensitivity in a 3D nasopharyngeal carcinoma model

Authors: Yanhua Fang, Shanshan Liang, Jianong Gao, Zhe Wang, Cheng Li, Ruoyu Wang, Weiting Yu

Published in: Cancer Cell International | Issue 1/2022

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Abstract

Purpose

Radiotherapy is one of the essential treatment modalities for nasopharyngeal carcinoma (NPC), however, radioresistance still poses challenges. Three-dimensional (3D) tumor culture models mimic the in vivo growth conditions of cells more accurately than 2D models. This study is to compare the tumor biological behaviors of NPC cells in 2D, On-Surface 3D and Embedded 3D systems, and to investigate the correlation between radioresistance and extracellular matrix (ECM) stiffness.

Methods

The morphology and radioresistance of the human NPC cell line CNE-1 were observed in 2D and 3D systems. The CCK-8 assay, wounding healing assays, flow cytometry, soft agar assays, and western blot analysis were used to evaluate differences in biological behaviors such as proliferation, migration, cell cycle distribution, and stem cell activity. Different ECM stiffness systems were established by co-blending collagen and alginate in varying proportions. ECM stiffness was evaluated by compressive elastic moduli measurement and colony formation assay was used to assess radioresistance of NPC cells in systems with different ECM stiffness after irradiation.

Results

Compared to 2D models, the morphology of NPC cells in 3D culture microenvironments has more in common with in vivo tumor cells and 3D cultured NPC cells exhibit stronger radioresistance. Integrin β1 but not the epithelial-to-mesenchymal transition pathway in 3D models boost migration ability. Cell proliferation was enhanced, the proportion of tumor stem cells was increased, and G1/S phase arrest occurred in 3D models. NPC cells cultured in softer ECM systems (with low alginate proportions) exhibit striking resistance to ionizing radiation.

Conclusion

The tumor biological behaviors of NPC cells in 3D groups were obviously different from that of 2D. Radioresistance of NPC cells increased with the stiffness of ECM decreasing.
Appendix
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Metadata
Title
Extracellular matrix stiffness mediates radiosensitivity in a 3D nasopharyngeal carcinoma model
Authors
Yanhua Fang
Shanshan Liang
Jianong Gao
Zhe Wang
Cheng Li
Ruoyu Wang
Weiting Yu
Publication date
01-12-2022
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2022
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-022-02787-5

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