Human 3D vascularized organotypic microfluidic assays to study breast cancer cell extravasation
Name
Jeon-2015-Human 3D vacularized.pdf
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1.22 MB
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Author(s)
Jeon, Jessie S.
Bersini, Simone
Gilardi, Mara
Dubini, Gabriele
Charest, Joseph L.
Moretti, Matteo
Kamm, Roger Dale
Date Issued
January 2015
Journal
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences (U.S.)
Citation
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.
Version
Final published version
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Mechanical Engineering
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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.
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DOI of Published Version
https://doi.org/10.1073/pnas.1417115112
