Bioengineered 3D platform to explore cell–ECM interactions and drug resistance of epithelial ovarian cancer cells

Autor: Matthias P. Lutolf, Dietmar W. Hutmacher, Kathryn S. Stok, Simone C. Rizzi, Judith A. Clements, Daniela Loessner
Rok vydání: 2010
Předmět:
Integrins
Cell viability
Cell
medicine.disease_cause
Cell morphology
Hydrogel
Polyethylene Glycol Dimethacrylate
Polyethylene Glycols
Biomimetic Materials
Cell encapsulation
Ovarian Neoplasms
biology
060106 Cellular Interactions (incl. Adhesion Matrix Cell Wall)
Hydrogels
Cell biology
medicine.anatomical_structure
Biomimetic material
Mechanics of Materials
Malignant Phenotype
Self-healing hydrogels
3-Dimensional Culture
Female
Oligopeptides
Paclitaxel
Cell Survival
Extracellular Matrices
Integrin
Biophysics
Bioengineering
Biomaterials
100404 Regenerative Medicine (incl. Stem Cells and Tissue Engineering)
Cell Line
Tumor
Spheroids
Cellular
medicine
Humans
Multicellular Tumor Spheroids
Breast-Cancer
Mechanical Phenomena
111201 Cancer Cell Biology
Ecm
Tissue
Mesothelial Cells
Carcinoma
Epithelial Cells
Antineoplastic Agents
Phytogenic
Hydrogel
Drug Resistance
Neoplasm
In-Vitro
Cell culture
Cancer cell
Ceramics and Composites
biology.protein
Carcinogenesis
Zdroj: Biomaterials
ISSN: 0142-9612
Popis: 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. Copyright © 2010 Elsevier Ltd. All rights reserved.
Databáze: OpenAIRE
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