Contact-dependent carcinoma aggregate dispersion by M2a macrophages via ICAM-1 and β2 integrin interactions
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: [email protected] 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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BibTeX
@article{bai2026contactdependent,
title = {{Contact-dependent carcinoma aggregate dispersion by M2a macrophages via ICAM-1 and β2 integrin interactions}},
author = {Jing Bai and Giulia Adriani and Truong-Minh Dang and Ting-Yuan Tu and Hwei-Xian Leong Penny and Siew-Cheng Wong and Roger D. Kamm and Jean-Paul Thiery},
journal = {Oncotarget},
year = {2026},
month = oct,
doi = {10.18632/oncotarget.4716},
url = {https://hal.science/hal-05776434v1},
note = {CC BY},
}
RIS
TY - JOUR
TI - Contact-dependent carcinoma aggregate dispersion by M2a macrophages via ICAM-1 and β2 integrin interactions
AU - Jing Bai
AU - Giulia Adriani
AU - Truong-Minh Dang
AU - Ting-Yuan Tu
AU - Hwei-Xian Leong Penny
AU - Siew-Cheng Wong
AU - Roger D. Kamm
AU - Jean-Paul Thiery
PY - 2026
DA - 2026/10/03
JO - Oncotarget
DO - 10.18632/oncotarget.4716
UR - https://hal.science/hal-05776434v1
AB - // 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: [email protected] 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.
SN - 1949-2553
ER -