Characterization of three-dimensional cancer cell migration in mixed collagen-Matrigel scaffolds using microfluidics and image analysis

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dc.contributor.author Anguiano, María
dc.contributor.author Castilla, Carlos
dc.contributor.author Maška, Martin
dc.contributor.author Ederra, Cristina
dc.contributor.author Peláez, Rafael
dc.contributor.author Morales, Xabier
dc.contributor.author Muñoz-Arrieta, Gorka
dc.contributor.author Mujika, Maite
dc.contributor.author Kozubek, Michal
dc.contributor.author Muñoz-Barrutia, Arrate
dc.contributor.author Rouzaut, Ana
dc.contributor.author Arana, Sergio
dc.contributor.author Garcia-Aznar, José Manuel
dc.contributor.author Ortiz de Solórzano, Carlos
dc.date.accessioned 2017-02-10T09:08:59Z
dc.date.available 2017-02-10T09:08:59Z
dc.date.issued 2017-02-06
dc.identifier.bibliographicCitation PLoS ONE, 2017, 12(2), pp. 1-24
dc.identifier.issn 1932-6203
dc.identifier.uri http://hdl.handle.net/10016/24160
dc.description.abstract Microfluidic devices are becoming mainstream tools to recapitulate in vitro the behavior of cells and tissues. In this study, we use microfluidic devices filled with hydrogels of mixed collagen-Matrigel composition to study the migration of lung cancer cells under different cancer invasion microenvironments. We present the design of the microfluidic device, characterize the hydrogels morphologically and mechanically and use quantitative image analysis to measure the migration of H1299 lung adenocarcinoma cancer cells in different experimental conditions. Our results show the plasticity of lung cancer cell migration, which turns from mesenchymal in collagen only matrices, to lobopodial in collagen-Matrigel matrices that approximate the interface between a disrupted basement membrane and the underlying connective tissue. Our quantification of migration speed confirms a biphasic role of Matrigel. At low concentration, Matrigel facilitates migration, most probably by providing a supportive and growth factor retaining environment. At high concentration, Matrigel slows down migration, possibly due excessive attachment. Finally, we show that antibody-based integrin blockade promotes a change in migration phenotype from mesenchymal or lobopodial to amoeboid and analyze the effect of this change in migration dynamics, in regards to the structure of the matrix. In summary, we describe and characterize a robust microfluidic platform and a set of software tools that can be used to study lung cancer cell migration under different microenvironments and experimental conditions. This platform could be used in future studies, thus benefitting from the advantages introduced by microfluidic devices: precise control of the environment, excellent optical properties, parallelization for high throughput studies and efficient use of therapeutic drugs.
dc.description.sponsorship We would like to acknowledge the support of the Spanish Ministry of Economy and Competitiveness, under grants number DPI2012-38090-C03-02 and DPI2015-64221-C2-2-R (COS), TEC2013-48552-C2-1-R, TEC2016-78052-R, TEC2015-73064-EXP (AMB) and the Torres Quevedo program PTQ-11-04778 (RP); the Spanish Ministry of Health (FIS PI13/02313) (AR); the Czech Science Foundation, under grant number 302/12/G157 (MK, MMaška); and the European Research Council (ERC) through project ERC-2012-StG 306751 (JMGA).
dc.format.extent 24
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher PLOS ONE
dc.rights © 2017, Authors
dc.rights Atribución 4.0 International
dc.rights.uri http://creativecommons.org/licenses/by/3.0/es/
dc.title Characterization of three-dimensional cancer cell migration in mixed collagen-Matrigel scaffolds using microfluidics and image analysis
dc.type article
dc.subject.eciencia Biología y Biomedicina
dc.subject.eciencia Medicina
dc.identifier.doi https://doi.org/10.1371/journal.pone.0171417
dc.rights.accessRights openAccess
dc.relation.projectID Gobierno de España. DPI2012-38090-C03-02
dc.relation.projectID Gobierno de España. DPI2015-64221-C2-2-R
dc.relation.projectID Gobierno de España. TEC2013-48552-C2-1-R
dc.relation.projectID Gobierno de España. TEC2016-78052-R
dc.relation.projectID Gobierno de España. TEC2015-73064-EXP
dc.relation.projectID Gobierno de España. FIS. PI13/02313
dc.relation.projectID Gobierno de España. INNCORPORA-PTQ-11-04778
dc.relation.projectID info:eu-repo/grantAgreement/ERC/2012-StG 306751/EU
dc.type.version publishedVersion
dc.identifier.publicationfirstpage 1
dc.identifier.publicationissue 2
dc.identifier.publicationlastpage 24
dc.identifier.publicationtitle PloS one
dc.identifier.publicationvolume 12
dc.identifier.uxxi AR/0000018732
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