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

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dc.affiliation.dptoUC3M. Departamento de Bioingenieríaes
dc.affiliation.grupoinvUC3M. Grupo de Investigación: BSEL - Laboratorio de Ciencia e Ingeniería Biomédicaes
dc.contributor.authorAnguiano, María
dc.contributor.authorCastilla, Carlos
dc.contributor.authorMaška, Martin
dc.contributor.authorEderra, Cristina
dc.contributor.authorPeláez, Rafael
dc.contributor.authorMorales, Xabier
dc.contributor.authorMuñoz-Arrieta, Gorka
dc.contributor.authorMujika, Maite
dc.contributor.authorKozubek, Michal
dc.contributor.authorMuñoz Barrutia, María Arrate
dc.contributor.authorRouzaut, Ana
dc.contributor.authorArana, Sergio
dc.contributor.authorGarcia-Aznar, José Manuel
dc.contributor.authorOrtiz de Solórzano, Carlos
dc.date.accessioned2017-02-10T09:08:59Z
dc.date.available2017-02-10T09:08:59Z
dc.date.issued2017-02-06
dc.description.abstractMicrofluidic 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.en
dc.description.sponsorshipWe 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).en
dc.format.extent24
dc.format.mimetypeapplication/pdf
dc.identifier.bibliographicCitationPLoS ONE, 2017, 12(2), pp. 1-24
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0171417
dc.identifier.issn1932-6203
dc.identifier.publicationfirstpage1
dc.identifier.publicationissue2
dc.identifier.publicationlastpage24
dc.identifier.publicationtitlePloS oneen
dc.identifier.publicationvolume12
dc.identifier.urihttps://hdl.handle.net/10016/24160
dc.identifier.uxxiAR/0000018732
dc.language.isoeng
dc.publisherPLOS ONE
dc.relation.projectIDGobierno de España. DPI2012-38090-C03-02es
dc.relation.projectIDGobierno de España. DPI2015-64221-C2-2-Res
dc.relation.projectIDGobierno de España. TEC2013-48552-C2-1-Res
dc.relation.projectIDGobierno de España. TEC2016-78052-Res
dc.relation.projectIDGobierno de España. TEC2015-73064-EXPes
dc.relation.projectIDGobierno de España. FIS. PI13/02313es
dc.relation.projectIDGobierno de España. INNCORPORA-PTQ-11-04778
dc.relation.projectIDinfo:eu-repo/grantAgreement/ERC/2012-StG 306751/EU
dc.rights© 2017, Authors
dc.rightsAtribución 4.0 International
dc.rights.accessRightsopen access
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/es/
dc.subject.ecienciaBiología y Biomedicinaes
dc.subject.ecienciaMedicinaes
dc.titleCharacterization of three-dimensional cancer cell migration in mixed collagen-Matrigel scaffolds using microfluidics and image analysisen
dc.typeresearch article*
dc.type.hasVersionVoR*
dspace.entity.typePublication
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