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dc.contributor.author
Håkanson, Maria
dc.contributor.author
Kobel, Stefan
dc.contributor.author
Lutolf, Matthias P.
dc.contributor.author
Textor, Marcus
dc.contributor.author
Cukierman, Edna
dc.contributor.author
Charnley, Mirren
dc.date.accessioned
2018-09-20T08:18:22Z
dc.date.available
2017-06-10T02:11:11Z
dc.date.available
2018-09-20T08:18:22Z
dc.date.issued
2012-06-29
dc.identifier.issn
1932-6203
dc.identifier.other
10.1371/journal.pone.0040141
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/51381
dc.identifier.doi
10.3929/ethz-b-000051381
dc.description.abstract
Background Increasing evidence shows that the cancer microenvironment affects both tumorigenesis and the response of cancer to drug treatment. Therefore in vitro models that selectively reflect characteristics of the in vivo environment are greatly needed. Current methods allow us to screen the effect of extrinsic parameters such as matrix composition and to model the complex and three-dimensional (3D) cancer environment. However, 3D models that reflect characteristics of the in vivo environment are typically too complex and do not allow the separation of discrete extrinsic parameters. Methodology/Principal Findings In this study we used a poly(ethylene glycol) (PEG) hydrogel-based microwell array to model breast cancer cell behavior in multilayer cell clusters that allows a rigorous control of the environment. The innovative array fabrication enables different matrix proteins to be integrated into the bottom surface of microwells. Thereby, extrinsic parameters including dimensionality, type of matrix coating and the extent of cell-cell adhesion could be independently studied. Our results suggest that cell to matrix interactions and increased cell-cell adhesion, at high cell density, induce independent effects on the response to Taxol in multilayer breast cancer cell clusters. In addition, comparing the levels of apoptosis and proliferation revealed that drug resistance mediated by cell-cell adhesion can be related to altered cell cycle regulation. Conversely, the matrix-dependent response to Taxol did not correlate with proliferation changes suggesting that cell death inhibition may be responsible for this effect. Conclusions/Significance The application of the PEG hydrogel platform provided novel insight into the independent role of extrinsic parameters controlling drug response. The presented platform may not only become a useful tool for basic research related to the role of the cancer microenvironment but could also serve as a complementary platform for in vitro drug development.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Public Library of Science
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/3.0/
dc.title
Controlled Breast Cancer Microarrays for the Deconvolution of Cellular Multilayering and Density Effects upon Drug Responses
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 3.0 Unported
ethz.journal.title
PLoS ONE
ethz.journal.volume
7
en_US
ethz.journal.issue
6
en_US
ethz.journal.abbreviated
PLoS ONE
ethz.pages.start
e40141
en_US
ethz.size
12 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.nebis
006206116
ethz.publication.place
s.l.
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02160 - Dep. Materialwissenschaft / Dep. of Materials::02646 - Institut für Polymere / Institute of Polymers::03389 - Spencer, Nicholas / Spencer, Nicholas
en_US
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02160 - Dep. Materialwissenschaft / Dep. of Materials::02646 - Institut für Polymere / Institute of Polymers::03389 - Spencer, Nicholas / Spencer, Nicholas
ethz.date.deposited
2017-06-10T02:11:33Z
ethz.source
ECIT
ethz.identifier.importid
imp59364f67d075e69175
ethz.ecitpid
pub:83842
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2017-07-12T14:10:57Z
ethz.rosetta.lastUpdated
2018-11-08T02:34:57Z
ethz.rosetta.versionExported
true
ethz.COinS
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