Contact-dependent carcinoma aggregate dispersion by M2a macrophages via ICAM-1 and β2 integrin interactions
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Bai-2015-Contact-dependent ca.pdf
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Author(s)
Bai, Jing
Adriani, Giulia
Dang, Truong-Minh
Tu, Ting-Yuan
Penny, Hwei-Xian Leong
Wong, Siew-Cheng
Thiery, Jean-Paul
Kamm, Roger Dale
Date Issued
July 2015
Journal
Oncotarget
Publisher
Impact Journals/National Center for Biotechnology Information (U.S.)
Citation
Bai, 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.
Version
Final published version
Abstract
Tumor-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.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Mechanical Engineering
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DOI of Published Version
https://doi.org/10.18632/oncotarget.4716
