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Cited by 110Immune cells in cancerCancer Cells and MetastasisCellular Mechanics and Interactions

Contact-dependent carcinoma aggregate dispersion by M2a macrophages via ICAM-1 and β2 integrin interactions

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Bai, Jing, Adriani, Giulia, Dang, Truong-Minh, Tu, Ting-Yuan, Leong Penny, Hwei-Xian, Wong, Siew-Cheng, Kamm, Roger D., Thiery, Jean-Paul·2015·Oncotarget
DOI 10.18632/oncotarget.4716PMC PMC4694832
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Abstract

// Jing Bai 1, 2, * , Giulia Adriani 1, * , Truong-Minh Dang 3 , Ting-Yuan Tu 1 , Hwei-Xian Leong Penny 3 , Siew-Cheng Wong 3 , Roger D. Kamm 1, 2 , Jean-Paul Thiery 1, 4, 5 1 BioSystems and Micromechanics IRG, Singapore-MIT Alliance for Research and Technology, 138602, Singapore 2 Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA 3 SIgN (Singapore Immunology Network), A*STAR (Agency for Science, Technology and Research), Biopolis, 138648, Singapore 4 Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 117597, Singapore 5 Institute of Molecular and Cell Biology, Proteos, 138673, Singapore * These authors have contributed equally to this work Correspondence to: Jean-Paul Thiery, e-mail: bchtjp@nus.edu.sg Keywords: epithelial-mesenchymal transition, microfluidics, macrophage phenotypes, macrophage polarization, cancer microenvironment Received: June 25, 2015 Accepted: July 17, 2015 Published: July 30, 2015 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.

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Authors
Bai, J., Adriani, G., Dang, T.-M., Tu, T.-Y., Leong Penny, H.-X., Wong, S.-C., Kamm, R. D., & Thiery, J.-P.
Affiliations
  • Singapore-MIT Alliance for Research and Technology (SG)
  • Agency for Science, Technology and Research (SG)
  • SIgN (Singapore Immunology Network), A*STAR (Agency for Science, Technology and Research), Biopolis, 138648, Singapore
  • National University of Singapore (SG)
Corresponding author
  • Bai, Jing
  • Adriani, Giulia
ORCID
Venue
Oncotarget
Publisher
Impact Journals, LLC
Published
2015-07-30
Volume
6
Issue
28
Pages
25295-25307
ISSN
1949-2553 (ISSN-L)
DOI
10.18632/oncotarget.4716
PMC
PMC4694832
OpenAlex
W2138086500
Cited by
110
References
3
Citations by year
2026: 5 · 2025: 5 · 2024: 3 · 2023: 5 · 2022: 10 · 2021: 12 · 2020: 20 · 2019: 14 · 2018: 10 · 2017: 10 · 2016: 14 · 2015: 2
FWCI
5.92
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Oncotarget (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by)
  • DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
  • HAL (submittedVersion)
Funders
  • National University of Singapore
  • Biomedical Research Council
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
  • Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
Keywords
tumor-associated macrophages, M2 macrophages, M1 macrophages, macrophage polarization, ICAM-1, beta2 integrins, tumor cell aggregates, epithelial-mesenchymal transition, tumor microenvironment, microfluidic co-culture, hydrogel scaffolds, endothelial monolayer
MeSH terms
Adenocarcinoma of Lung, Adenocarcinoma, Cell Communication, Cell Movement, Humans, Lung Neoplasms, Macrophages, Phenotype, Time Factors, Transfection, Signal Transduction, Intercellular Adhesion Molecule-1, CD18 Antigens, Coculture Techniques, Hydrogels, Cell Line, Tumor, Lab-On-A-Chip Devices, Epithelial-Mesenchymal Transition, Tumor Microenvironment, Human Umbilical Vein Endothelial Cells

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