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Cited by 139Cellular Mechanics and InteractionsHydrogels: synthesis, properties, applications3D Printing in Biomedical Research

3D extracellular matrix interactions modulate tumour cell growth, invasion and angiogenesis in engineered tumour microenvironments

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Taubenberger, Anna V., Bray, Laura J., Haller, Barbara, Shaposhnykov, Artem, Binner, Marcus, Freudenberg, Uwe, Guck, Jochen, Werner, Carsten·2016·Acta Biomaterialia
DOI 10.1016/j.actbio.2016.03.017
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Abstract

UNLABELLED: Interactions between tumour cells and extracellular matrix proteins of the tumour microenvironment play crucial roles in cancer progression. So far, however, there are only a few experimental platforms available that allow us to study these interactions systematically in a mechanically defined three-dimensional (3D) context. Here, we have studied the effect of integrin binding motifs found within common extracellular matrix (ECM) proteins on 3D breast (MCF-7) and prostate (PC-3, LNCaP) cancer cell cultures, and co-cultures with endothelial and mesenchymal stromal cells. For this purpose, matrix metalloproteinase-degradable biohybrid poly(ethylene) glycol-heparin hydrogels were decorated with the peptide motifs RGD, GFOGER (collagen I), or IKVAV (laminin-111). Over 14days, cancer spheroids of 100-200μm formed. While the morphology of poorly invasive MCF-7 and LNCaP cells was not modulated by any of the peptide motifs, the aggressive PC-3 cells exhibited an invasive morphology when cultured in hydrogels comprising IKVAV and GFOGER motifs compared to RGD motifs or nonfunctionalised controls. PC-3 (but not MCF-7 and LNCaP) cell growth and endothelial cell infiltration were also significantly enhanced in IKVAV and GFOGER presenting gels. Taken together, we have established a 3D culture model that allows for dissecting the effect of biochemical cues on processes relevant to early cancer progression. These findings provide a basis for more mechanistic studies that may further advance our understanding of how ECM modulates cancer cell invasion and how to ultimately interfere with this process. STATEMENT OF SIGNIFICANCE: Threedimensional in vitro cancer models have generated great interest over the past decade. However, most models are not suitable to systematically study the effects of environmental cues on cancer development and progression. To overcome this limitation, we have developed an innovative hydrogel platform to study the interactions between breast and prostate cancer cells and extracellular matrix ligands relevant to the tumour microenvironment. Our results show that hydrogels with laminin- and collagen-derived adhesive peptides induce a malignant phenotype in a cell-line specific manner. Thus, we have identified a method to control the incorporation of biochemical cues within a three dimensional culture model and anticipate that it will help us in better understanding the effects of the tumour microenvironment on cancer progression.

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  • The morphology-based classification allows quantification of the tumorigenic potential of different cell lines.

    “This morphology-based classification allows the quantification of the tumorigenic potential of different cell lines and the quick visualization of different conditions.”

    From Direct transfection of clonal organoids in Matrigel microbeads: a promising approach toward organoid-based genetic screens (2018) · cites this paper as [27]

    Section 3.2 classifies spheroid morphologies across MCF-7, LNCaP and PC-3 cell lines and quantifies the categories, identifying category IV as an invasive, aggressive phenotype. This supports using the classification to compare morphology and invasion, but the paper does not establish it as a measure of overall tumorigenic potential. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • Morphological classification can be used as a quick and reliable read-out to discriminate organoid features and gene functions, as previously described.

    “Here, we used morphological classification as a quick and reliable read-out to discriminate organoid features and gene functions, as previously described (27).”

    From Direct transfection of clonal organoids in Matrigel microbeads: a promising approach toward organoid-based genetic screens (2018) · cites this paper as [27]

    Section 3.2 classifies tumour spheroids by morphology and uses the categories to distinguish invasive from non-invasive phenotypes. The paper does not establish morphological classification as a quick and reliable read-out for organoid features or gene functions; it studies tumour spheroids and ECM conditions instead. Page numbers were not available in our copy. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

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Authors
Taubenberger, A. V., Bray, L. J., Haller, B., Shaposhnykov, A., Binner, M., Freudenberg, U., Guck, J., & Werner, C.
Affiliations
  • Biotechnologisches Zentrum (DE)
  • Queensland University of Technology (AU)
  • Max Bergmann Center of Biomaterials (DE)
Corresponding author
Taubenberger, Anna V.
ORCID
Venue
Acta Biomaterialia
Publisher
Elsevier BV
Published
2016-05
Volume
36
Pages
73-85
ISSN
1742-7061 (ISSN-L)
DOI
10.1016/j.actbio.2016.03.017
OpenAlex
W2294779059
Cited by
139
References
1
Citations by year
2026: 6 · 2025: 12 · 2024: 5 · 2023: 12 · 2022: 13 · 2021: 12 · 2020: 22 · 2019: 16 · 2018: 19 · 2017: 17 · 2016: 5
FWCI
13.07
Type
journal article
Language
en
Open access
Licence
Locations
  • Acta Biomaterialia (publishedVersion, other-oa)
  • PubMed (publishedVersion)
  • QUT ePrints (Queensland University of Technology) (submittedVersion, cc-by-nc-nd)
  • MPG.PuRe (Max Planck Society) (submittedVersion)
Funders
  • German Research Foundation (SFB-TR 67, WE 2539-7, FOR/EXC999)
  • Leibniz Association (SAW-2011-IPF-2 68)
  • European Union
  • Humboldt Foundation
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
  • Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
Keywords
extracellular matrix, tumor microenvironment, integrin-binding motif, RGD peptide, IKVAV peptide, laminin-111, type I collagen, biohybrid hydrogels, tumor spheroids, tumor invasion, tumor angiogenesis, breast cancer, prostate cancer
MeSH terms
Breast Neoplasms, Extracellular Matrix, Female, Humans, Male, Models, Biological, Neovascularization, Pathologic, Peptides, Prostatic Neoplasms, Hydrogels, Tumor Microenvironment, MCF-7 Cells

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