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A multi-site metastasis-on-a-chip microphysiological system for assessing metastatic preference of cancer cells
Julio Aleman1, Aleksander Skardal1,2,3,4,5
1Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Medical Center, 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.
Insights
This study introduces a novel metastasis-on-a-chip device using 3D organoids to model cancer spread. The platform successfully tracks colorectal cancer (CRC) cells migrating to liver and lung models, mimicking human metastasis patterns.
Area of Science:
- Biomedical Engineering
- Cancer Research
- Microfluidics
Background:
- Metastatic disease is a major cause of cancer mortality.
- Existing in vitro models often overlook metastasis, focusing on primary tumors.
- Understanding cancer cell dissemination is crucial for developing effective treatments.
Purpose of the Study:
- To develop and validate a metastasis-on-a-chip device for studying cancer cell migration.
- To create a platform that mimics the in vivo microenvironment for metastasis research.
- To investigate the preferential homing of colorectal cancer cells to specific organs.
Main Methods:
- Fabrication of a microfluidic device housing multiple bioengineered 3D organoids.
- Utilized 3D photopatterning with extracellular matrix-derived hydrogels.
- Incorporated colorectal cancer (CRC) organoids connected to liver, lung, and endothelial cell constructs.
- Employed recirculating fluid flow to simulate circulation and tracked fluorescently labeled cancer cells.
Main Results:
- The metastasis-on-a-chip device successfully cultured and monitored cancer cell behavior.
- HCT116 CRC cells demonstrated preferential migration and homing to liver and lung organoid constructs.
- Observed metastasis patterns mirrored common metastatic sites for colorectal cancer in patients.
Conclusions:
- The developed platform provides a robust in vitro model for studying cancer metastasis.
- This technology can elucidate mechanisms of cancer cell dissemination and organotropism.
- Future applications may identify novel therapeutic targets for preventing or treating metastatic disease.
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