Cited by 19Hydrogels: synthesis, properties, applicationsCancer Cells and MetastasisCellular Mechanics and Interactions

Expansion of Ovarian Cancer Stem-like Cells in Poly(ethylene glycol)-Cross-Linked Poly(methyl vinyl ether-alt-maleic acid) and Alginate Double-Network Hydrogels

Zhou, Naizhen, Ma, Xiaoe, Bernaerts, Katrien V., Ren, Pengfei, Hu, Wanjun, Zhang, Tianzhu·2020·ACS Biomaterials Science & Engineering

Abstract

A better understanding of cancer stem cells (CSCs) is essential for research on cancer therapy and drug resistance. Currently, increasingly more investigations are focused on obtaining CSCs to study the mechanism of their enhanced malignancy. In this work, three kinds of double-network hydrogels (PEMM/alginate), consisting of poly(ethylene glycol) (PEG) covalently cross-linked poly(methyl vinyl ether- alt -maleic acid) (P(MVE- alt -MA)) (network 1, denoted as PEMM) and Sr 2+ (or Ca 2+, Fe 3+ ) ionically cross-linked alginates (network 2, denoted as SrAlg, CaAlg, or FeAlg), were prepared. The stiffness, morphology, and components of the PEMM/alginate hydrogels were systematically investigated to understand their effects on CSC enrichment. Only the PEMM/FeAlg hydrogels could support the long-term growth, proliferation, and spheroid formation of SK-OV-3 cells. The expression of CSC-related markers was evaluated with the levels of protein and gene at different stages. The cell spheroids cultured in the PEMM/FeAlg hydrogels acquired certain CSC-like properties, thus drug resistance was enhanced, especially in the PEMM-1/FeAlg hydrogel. In vivo tumorigenicity experiments also confirmed the presence of more CSCs in the PEMM-1/FeAlg hydrogel. The results suggest that matrix stiffness, morphology, and cations act synergistically on the regulation of the epithelial–mesenchymal transition (EMT), interleukin-6 (IL-6), and Wnt pathways, affecting the invasiveness of ovarian cancer and the conversion of the non-CSCs into CSCs. The PEMM-1/FeAlg hydrogel with lower elastic modulus, a more macroporous morphology, and higher swelling rate can significantly enhance the stemness, malignancy, and tumorigenicity of SK-OV-3 cells.

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Crossref · 10.1021/acsbiomaterials.9b01967

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  • A double network of alginate and polyethylene glycol (PEG)-based hydrogels was shown to increase doxorubicin resistance and CSC markers in SK-OV-3 cells compared to 2D cultures.

    “A double network of alginate and polyethylene glycol (PEG)-based hydrogels was shown to increase doxorubicin resistance and CSC markers in SK-OV-3 cells compared to 2D cultures (Zhou et al., 2020).”
  • PEG-crosslinked poly(methyl vinyl ether-alt-maleic acid) or PEMM/alginate network hydrogels induced EMT, a CSC-like phenotype and chemoresistance in encapsulated SK-OV-3 spheroids, driven by hydrogel stiffness, porosity and cation of choice for crosslinking.

    “PEG-crosslinked poly(methyl vinyl ether-alt-maleic acid) or PEMM/alginate network hydrogels induced EMT, a CSC-like phenotype and chemoresistance in encapsulated SK-OV-3 spheroids, driven by hydrogel stiffness, porosity and cation of choice for crosslinking (Zhou et al., 2020).”

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Authors
Zhou, N., Ma, X., Bernaerts, K. V., Ren, P., Hu, W., & Zhang, T.
Affiliations
  • State Key Laboratory of Digital Medical Engineering (CN)
  • Maastricht University (NL)
Corresponding author
Zhang, Tianzhu
Venue
ACS Biomaterials Science & Engineering
Published
2020-04-09
Volume
6
Issue
6
Pages
3310-3326
ISSN
2373-9878 (ISSN-L)
OpenAlex
W3015485718
Cited by
19
References
85
Citations by year
2026: 2 · 2025: 3 · 2024: 3 · 2023: 2 · 2022: 5 · 2021: 2 · 2020: 2
FWCI
0.92
Type
journal article
Language
en
Open access
closed
Locations
  • ACS Biomaterials Science & Engineering (publishedVersion)
  • PubMed (publishedVersion)
  • Research Publications (Maastricht University) (publishedVersion)
  • Research Publications (Maastricht University) (submittedVersion)
Funders
  • Ministry of Education of the People's Republic of China
  • Ministry of Science and Technology of the People's Republic of China (2011YQ03013403)
  • National Natural Science Foundation of China (81600407)
  • Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
  • Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
Keywords
double-network hydrogel, alginate, ionic crosslinking, extracellular matrix stiffness, cell spheroids, drug resistance, epithelial-mesenchymal transition, interleukin-6, Wnt signaling, tumorigenicity, SKOV3 cells, stemness
MeSH terms
Alginates, Female, Humans, Maleic Anhydrides, Ovarian Neoplasms, Polyethylene Glycols, Polyvinyls, Neoplastic Stem Cells, Hydrogels

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