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Biotechnol Bioeng. 2019 Apr;116(4):936-944. doi: 10.1002/bit.26871. Epub 2018 Dec 31.

A multi-site metastasis-on-a-chip microphysiological system for assessing metastatic preference of cancer cells.

Aleman J1, Skardal A1,2,3,4,5.

Author information

1
Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Medical Center, Winston-Salem, North Carolina.
2
Virginia Tech-Wake Forest School of Biomedical Engineering and Sciences, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina.
3
Department of Cancer Biology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina.
4
Department of Molecular Medicine and Translational Science, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina.
5
Comprehensive Cancer Center at Wake Forest Baptist Medical, Medical Center Boulevard, Winston-Salem, North Carolina.

Abstract

Metastatic disease remains one of the primary reasons for cancer-related deaths, yet the majority of in vitro cancer models focus on the primary tumor sites. Here, we describe a metastasis-on-a-chip device that houses multiple bioengineered three-dimensional (3D) organoids, established by a 3D photopatterning technique employing extracellular matrix-derived hydrogel biomaterials. Specifically, cancer cells begin in colorectal cancer (CRC) organoid, which resides in a single microfluidic chamber connected to multiple downstream chambers in which liver, lung, and endothelial constructs are housed. Under recirculating fluid flow, tumor cells grow in the primary site, eventually enter circulation, and can be tracked via fluorescent imaging. Importantly, we describe that in the current version of this platform, HCT116 CRC cells preferentially home to the liver and lung constructs; the corresponding organs of which CRC metastases arise the most in human patients. We believe that in subsequent studies this platform can be implemented to better understand the mechanisms underlying metastasis, perhaps resulting in the identification of targets for intervention.

KEYWORDS:

cancer; microfluidics; organ-on-a-chip; three-dimensional (3D) in vitro model; tumor-on-a-chip

PMID:
30450540
PMCID:
PMC6399040
[Available on 2020-04-01]
DOI:
10.1002/bit.26871

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