Contact-dependent carcinoma aggregate dispersion by M2a macrophages via ICAM-1 and β2 integrin interactions
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 producti...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Impact Journals/National Center for Biotechnology Information (U.S.)
2017
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| Online Access: | http://hdl.handle.net/1721.1/108200 https://orcid.org/0000-0002-7232-304X |
| _version_ | 1826192326389661696 |
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| author | Dang, Truong-Minh Tu, Ting-Yuan Penny, Hwei-Xian Leong Wong, Siew-Cheng Thiery, Jean-Paul Bai, Jing Adriani, Giulia Kamm, Roger Dale |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Dang, Truong-Minh Tu, Ting-Yuan Penny, Hwei-Xian Leong Wong, Siew-Cheng Thiery, Jean-Paul Bai, Jing Adriani, Giulia Kamm, Roger Dale |
| author_sort | Dang, Truong-Minh |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T09:09:27Z |
| format | Article |
| id | mit-1721.1/108200 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T09:09:27Z |
| publishDate | 2017 |
| publisher | Impact Journals/National Center for Biotechnology Information (U.S.) |
| record_format | dspace |
| spelling | mit-1721.1/1082002022-09-30T13:52:41Z Contact-dependent carcinoma aggregate dispersion by M2a macrophages via ICAM-1 and β2 integrin interactions Dang, Truong-Minh Tu, Ting-Yuan Penny, Hwei-Xian Leong Wong, Siew-Cheng Thiery, Jean-Paul Bai, Jing Adriani, Giulia Kamm, Roger Dale Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Mechanical Engineering Bai, Jing Adriani, Giulia Kamm, Roger Dale 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. Singapore-MIT Alliance for Research and Technology (SMART - BioSym IRG) National University of Singapore. Biochemistry department Singapore. Biomedical Research Council Singapore. Agency for Science, Technology and Research 2017-04-18T11:56:44Z 2017-04-18T11:56:44Z 2015-07 2015-06 Article http://purl.org/eprint/type/JournalArticle 1949-2553 http://hdl.handle.net/1721.1/108200 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. https://orcid.org/0000-0002-7232-304X en_US http://dx.doi.org/10.18632/oncotarget.4716 Oncotarget Creative Commons Attribution 3.0 Unported license http://creativecommons.org/licenses/by/3.0/ application/pdf Impact Journals/National Center for Biotechnology Information (U.S.) Impact Journals |
| spellingShingle | Dang, Truong-Minh Tu, Ting-Yuan Penny, Hwei-Xian Leong Wong, Siew-Cheng Thiery, Jean-Paul Bai, Jing Adriani, Giulia Kamm, Roger Dale Contact-dependent carcinoma aggregate dispersion by M2a macrophages via ICAM-1 and β2 integrin interactions |
| title | Contact-dependent carcinoma aggregate dispersion by M2a macrophages via ICAM-1 and β2 integrin interactions |
| title_full | Contact-dependent carcinoma aggregate dispersion by M2a macrophages via ICAM-1 and β2 integrin interactions |
| title_fullStr | Contact-dependent carcinoma aggregate dispersion by M2a macrophages via ICAM-1 and β2 integrin interactions |
| title_full_unstemmed | Contact-dependent carcinoma aggregate dispersion by M2a macrophages via ICAM-1 and β2 integrin interactions |
| title_short | Contact-dependent carcinoma aggregate dispersion by M2a macrophages via ICAM-1 and β2 integrin interactions |
| title_sort | contact dependent carcinoma aggregate dispersion by m2a macrophages via icam 1 and β2 integrin interactions |
| url | http://hdl.handle.net/1721.1/108200 https://orcid.org/0000-0002-7232-304X |
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