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dc.contributor.authorBai, Jing
dc.contributor.authorAdriani, Giulia
dc.contributor.authorDang, Truong-Minh
dc.contributor.authorTu, Ting-Yuan
dc.contributor.authorPenny, Hwei-Xian Leong
dc.contributor.authorWong, Siew-Cheng
dc.contributor.authorThiery, Jean-Paul
dc.contributor.authorKamm, Roger Dale
dc.date.accessioned2015-11-04T13:19:50Z
dc.date.available2015-11-04T13:19:50Z
dc.date.issued2015-07
dc.date.submitted2015-06
dc.identifier.issn1949-2553
dc.identifier.urihttp://hdl.handle.net/1721.1/99698
dc.description.abstractTumor-associated macrophages (TAMs) can constitute up to 50% of the tumor mass and have strong implications in tumor progression and metastasis. Macrophages are plastic and can polarize to various subtypes that differ in terms of surface receptor expression as well as cytokine and chemokine production and effector function. Conventionally, macrophages are grouped into two major subtypes: the classically activated M1 macrophages and the alternatively activated M2 macrophages. M1 macrophages are pro-inflammatory, promote T helper (Th) 1 responses, and show tumoricidal activity, whereas M2 macrophages contribute to tissue repair and promote Th2 responses. Herein, we present a microfluidic system integrating tumor cell aggregates and subtypes of human monocyte-derived macrophages in a three-dimensional hydrogel scaffold, in close co-culture with an endothelial monolayer to create an in vitro tumor microenvironment. This platform was utilized to study the role of individual subtypes of macrophages (M0, M1, M2a, M2b and M2c) in human lung adenocarcinoma (A549) aggregate dispersion, as a representation of epithelial-mesenchymal transition (EMT). A significant difference was observed when M2a macrophages were in direct contact with or separated from A549 aggregates, suggesting a possible mechanism for proximity-induced, contact-dependent dissemination via ICAM-1 and integrin β2 interactions. Indeed, M2a macrophages tended to infiltrate and release cells from carcinoma cell aggregates. These findings may help in the development of immunotherapies based on enhancing the tumor-suppressive properties of TAMs.en_US
dc.description.sponsorshipSingapore-MIT Alliance for Research and Technologyen_US
dc.description.sponsorshipNational University of Singaporeen_US
dc.description.sponsorshipSingapore. Biomedical Research Councilen_US
dc.language.isoen_US
dc.publisherImpact Journals/National Center for Biotechnology Information (U.S.)en_US
dc.relation.isversionofhttp://dx.doi.org/10.18632/oncotarget.4716en_US
dc.rightsCreative Commons Attributionen_US
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/en_US
dc.sourceImpact Journals/National Center for Biotechnology Information (U.S.)en_US
dc.titleContact-dependent carcinoma aggregate dispersion by M2a macrophages via ICAM-1 and β2 integrin interactionsen_US
dc.typeArticleen_US
dc.identifier.citationBai, Jing, Giulia Adriani, Truong-Minh Dang, Ting-Yuan Tu, Hwei-Xian Leong Penny, Siew-Cheng Wong, Roger D. Kamm, and Jean-Paul Thiery. “Contact-Dependent Carcinoma Aggregate Dispersion by M2a Macrophages via ICAM-1 and Β2 Integrin Interactions.” Oncotarget 6, no. 28 (September 21, 2015): 25295–25307.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biological Engineeringen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Mechanical Engineeringen_US
dc.contributor.mitauthorBai, Jingen_US
dc.contributor.mitauthorKamm, Roger Daleen_US
dc.relation.journalOncotargeten_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsBai, Jing; Adriani, Giulia; Dang, Truong-Minh; Tu, Ting-Yuan; Penny, Hwei-Xian Leong; Wong, Siew-Cheng; Kamm, Roger D.; Thiery, Jean-Paulen_US
dc.identifier.orcidhttps://orcid.org/0000-0002-7232-304X
mit.licensePUBLISHER_CCen_US
mit.metadata.statusComplete


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