Bioengineered 3D platform to explore cell-ECM interactions and drug resistance of epithelial ovarian cancer cells.
By D. Loessner, K. Stok, M. Lutolf, Dietmar Werner Hutmacher, J. Clements, S. Rizzi. Biomaterials, 2010
597 citations recorded by the source corpus.
The behaviour of cells cultured within three-dimensional (3D) structures rather than onto two-dimensional (2D) culture plastic more closely reflects their in vivo responses. Consequently, 3D culture systems are becoming crucial scientific tools in cancer cell research. We used a novel 3D culture concept to assess cell-matrix interactions implicated in carcinogenesis: a synthetic hydrogel matrix equipped with key biomimetic features, namely incorporated cell integrin-binding motifs (e.g. RGD peptides) and the ability of being degraded by cell-secreted proteases (e.g. matrix metalloproteases). As a cell model, we chose epithelial ovarian cancer, an aggressive disease typically diagnosed at an advanced stage when chemoresistance occurs. Both cell lines used (OV-MZ-6, SKOV-3) proliferated similarly in 2D, but not in 3D. Spheroid formation was observed exclusively in 3D when cells were embedded within hydrogels. By exploiting the design flexibility of the hydrogel characteristics, we showed that proliferation in 3D was dependent on cell-integrin engagement and the ability of cells to proteolytically remodel their extracellular microenvironment. Higher survival rates after exposure to the anti-cancer drug paclitaxel were observed in cell spheroids grown in hydrogels (40-60%) compared to cell monolayers in 2D (20%). Thus, 2D evaluation of chemosensitivity may not reflect pathophysiological events seen in patients. Because of the design flexibility of their characteristics and their stability in long-term cultures (28 days), these biomimetic hydrogels represent alternative culture systems for the increasing demand in cancer research for more versatile, physiologically relevant and reproducible 3D matrices.
Subfields: Biomedical Engineering, Cell Biology, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/73429d3175b8535e8bb53535a96f8f1f9bf94136
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
In Biomedical Engineering
- F. Melchels
- Ali Khademhosseini
- K. Yue
- R. Edmondson
- Audrey F. Adcock
- Dietmar Werner Hutmacher
- Liju Yang
- Jessica Jenkins Broglie
In Cell Biology
In Molecular Biology
Citations in the corpus
- Three-Dimensional Cell Culture Systems and Their Applications in Drug Discovery and Cell-Based Biosensors (2014, background): “(2010) reported that ovarian cancer cells in 3D culture had significantly increased levels of mRNA expression of the cell surface receptors a3/a5/b1 integrins and the protease MMP9 compared to cells in 2D culture.(41) In prostate cancer cells, the chemokine derived factor 1-alpha (SDF-1a), its prima”
- Functionalization, preparation and use of cell-laden gelatin methacryloyl–based hydrogels as modular tissue culture platforms (2016, methodology): “Our team has optimized the application of two quantitative assays to 3D cell cultures in which cells are embedded within different hydrogel materials 13,23 .”
- 3D Cell Culture Systems: Advantages and Applications (2015, background): “The effects of anticancer drugs doxorubicin and paclitaxel were markedly different when cells were exposed to them in the 2D and 3D systems (Loessner et al., 2010; MillerotSerrurot et al., 2010).”