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

Abstract 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 cu...

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Published inBiomaterials Vol. 31; no. 32; pp. 8494 - 8506
Main Authors Loessner, Daniela, Stok, Kathryn S, Lutolf, Matthias P, Hutmacher, Dietmar W, Clements, Judith A, Rizzi, Simone C
Format Journal Article
LanguageEnglish
Published Netherlands Elsevier Ltd 01.11.2010
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Abstract Abstract 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.
AbstractList Abstract 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.
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.
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.
Author Loessner, Daniela
Hutmacher, Dietmar W
Clements, Judith A
Rizzi, Simone C
Lutolf, Matthias P
Stok, Kathryn S
Author_xml – sequence: 1
  fullname: Loessner, Daniela
– sequence: 2
  fullname: Stok, Kathryn S
– sequence: 3
  fullname: Lutolf, Matthias P
– sequence: 4
  fullname: Hutmacher, Dietmar W
– sequence: 5
  fullname: Clements, Judith A
– sequence: 6
  fullname: Rizzi, Simone C
BackLink https://www.ncbi.nlm.nih.gov/pubmed/20709389$$D View this record in MEDLINE/PubMed
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Snippet Abstract The behaviour of cells cultured within three-dimensional (3D) structures rather than onto two-dimensional (2D) culture plastic more closely reflects...
The behaviour of cells cultured within three-dimensional (3D) structures rather than onto two-dimensional (2D) culture plastic more closely reflects their in...
The behaviour of cells cultured within three-dimensional (3D) structures rather than onto two-dimensional (2D) culture plastic more closely reflects their in...
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StartPage 8494
SubjectTerms Advanced Basic Science
Antineoplastic Agents, Phytogenic - pharmacology
Bioengineering
Biomimetic material
Biomimetic Materials - chemistry
Biomimetic Materials - metabolism
Cell encapsulation
Cell Line, Tumor
Cell morphology
Cell Survival - drug effects
Cell viability
Dentistry
Drug Resistance, Neoplasm
ECM
Epithelial Cells - cytology
Epithelial Cells - metabolism
Female
Humans
Hydrogel
Hydrogel, Polyethylene Glycol Dimethacrylate - chemistry
Hydrogel, Polyethylene Glycol Dimethacrylate - metabolism
Integrins - metabolism
Mechanical Phenomena
Oligopeptides - chemistry
Oligopeptides - metabolism
Ovarian Neoplasms - drug therapy
Ovarian Neoplasms - metabolism
Paclitaxel - pharmacology
Polyethylene Glycols - chemistry
Polyethylene Glycols - metabolism
Spheroids, Cellular - cytology
Title Bioengineered 3D platform to explore cell–ECM interactions and drug resistance of epithelial ovarian cancer cells
URI https://www.clinicalkey.es/playcontent/1-s2.0-S0142961210009075
https://dx.doi.org/10.1016/j.biomaterials.2010.07.064
https://www.ncbi.nlm.nih.gov/pubmed/20709389
https://search.proquest.com/docview/759315367
Volume 31
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