Human 3D vascularized organotypic microfluidic assays to study breast cancer cell extravasation
A key aspect of cancer metastases is the tendency for specific cancer cells to home to defined subsets of secondary organs. Despite these known tendencies, the underlying mechanisms remain poorly understood. Here we develop a microfluidic 3D in vitro model to analyze organ-specific human breast canc...
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| Format: | Article |
| Language: | en_US |
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National Academy of Sciences (U.S.)
2015
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| Online Access: | http://hdl.handle.net/1721.1/98037 https://orcid.org/0000-0002-7232-304X |
| _version_ | 1811070137300680704 |
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| author | Jeon, Jessie S. Bersini, Simone Gilardi, Mara Dubini, Gabriele Charest, Joseph L. Moretti, Matteo Kamm, Roger Dale |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Jeon, Jessie S. Bersini, Simone Gilardi, Mara Dubini, Gabriele Charest, Joseph L. Moretti, Matteo Kamm, Roger Dale |
| author_sort | Jeon, Jessie S. |
| collection | MIT |
| description | A key aspect of cancer metastases is the tendency for specific cancer cells to home to defined subsets of secondary organs. Despite these known tendencies, the underlying mechanisms remain poorly understood. Here we develop a microfluidic 3D in vitro model to analyze organ-specific human breast cancer cell extravasation into bone- and muscle-mimicking microenvironments through a microvascular network concentrically wrapped with mural cells. Extravasation rates and microvasculature permeabilities were significantly different in the bone-mimicking microenvironment compared with unconditioned or myoblast containing matrices. Blocking breast cancer cell A[subscript 3] adenosine receptors resulted in higher extravasation rates of cancer cells into the myoblast-containing matrices compared with untreated cells, suggesting a role for adenosine in reducing extravasation. These results demonstrate the efficacy of our model as a drug screening platform and a promising tool to investigate specific molecular pathways involved in cancer biology, with potential applications to personalized medicine. |
| first_indexed | 2024-09-23T08:27:10Z |
| format | Article |
| id | mit-1721.1/98037 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T08:27:10Z |
| publishDate | 2015 |
| publisher | National Academy of Sciences (U.S.) |
| record_format | dspace |
| spelling | mit-1721.1/980372022-09-30T09:19:07Z Human 3D vascularized organotypic microfluidic assays to study breast cancer cell extravasation Jeon, Jessie S. Bersini, Simone Gilardi, Mara Dubini, Gabriele Charest, Joseph L. Moretti, Matteo Kamm, Roger Dale Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Mechanical Engineering Jeon, Jessie S. Kamm, Roger Dale A key aspect of cancer metastases is the tendency for specific cancer cells to home to defined subsets of secondary organs. Despite these known tendencies, the underlying mechanisms remain poorly understood. Here we develop a microfluidic 3D in vitro model to analyze organ-specific human breast cancer cell extravasation into bone- and muscle-mimicking microenvironments through a microvascular network concentrically wrapped with mural cells. Extravasation rates and microvasculature permeabilities were significantly different in the bone-mimicking microenvironment compared with unconditioned or myoblast containing matrices. Blocking breast cancer cell A[subscript 3] adenosine receptors resulted in higher extravasation rates of cancer cells into the myoblast-containing matrices compared with untreated cells, suggesting a role for adenosine in reducing extravasation. These results demonstrate the efficacy of our model as a drug screening platform and a promising tool to investigate specific molecular pathways involved in cancer biology, with potential applications to personalized medicine. National Cancer Institute (U.S.) (Grant R33 CA174550-01) National Cancer Institute (U.S.) (Grant R21 CA140096) Italian Ministry of Health Charles Stark Draper Laboratory (Fellowship) 2015-08-05T16:14:35Z 2015-08-05T16:14:35Z 2015-01 2014-09 Article http://purl.org/eprint/type/JournalArticle 0027-8424 1091-6490 http://hdl.handle.net/1721.1/98037 Jeon, Jessie S., Simone Bersini, Mara Gilardi, Gabriele Dubini, Joseph L. Charest, Matteo Moretti, and Roger D. Kamm. “Human 3D Vascularized Organotypic Microfluidic Assays to Study Breast Cancer Cell Extravasation.” Proc Natl Acad Sci USA 112, no. 1 (December 18, 2014): 214–219. https://orcid.org/0000-0002-7232-304X en_US http://dx.doi.org/10.1073/pnas.1417115112 Proceedings of the National Academy of Sciences Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf National Academy of Sciences (U.S.) National Academy of Sciences (U.S.) |
| spellingShingle | Jeon, Jessie S. Bersini, Simone Gilardi, Mara Dubini, Gabriele Charest, Joseph L. Moretti, Matteo Kamm, Roger Dale Human 3D vascularized organotypic microfluidic assays to study breast cancer cell extravasation |
| title | Human 3D vascularized organotypic microfluidic assays to study breast cancer cell extravasation |
| title_full | Human 3D vascularized organotypic microfluidic assays to study breast cancer cell extravasation |
| title_fullStr | Human 3D vascularized organotypic microfluidic assays to study breast cancer cell extravasation |
| title_full_unstemmed | Human 3D vascularized organotypic microfluidic assays to study breast cancer cell extravasation |
| title_short | Human 3D vascularized organotypic microfluidic assays to study breast cancer cell extravasation |
| title_sort | human 3d vascularized organotypic microfluidic assays to study breast cancer cell extravasation |
| url | http://hdl.handle.net/1721.1/98037 https://orcid.org/0000-0002-7232-304X |
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