Human colorectal cancer-on-chip model to study the microenvironmental influence on early metastatic spread
Summary: Colorectal cancer (CRC) progression is a complex process that is not well understood. We describe an in vitro organ-on-chip model that emulates in vivo tissue structure and the tumor microenvironment (TME) to better understand intravasation, an early step in metastasis. The CRC-on-chip inco...
| Main Authors: | , , , , , , , , , , , |
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| פורמט: | Article |
| שפה: | English |
| יצא לאור: |
Elsevier
2021-05-01
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| סדרה: | iScience |
| נושאים: | |
| גישה מקוונת: | http://www.sciencedirect.com/science/article/pii/S2589004221004776 |
| _version_ | 1829515046219153408 |
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| author | Carly Strelez Sujatha Chilakala Kimya Ghaffarian Roy Lau Erin Spiller Nolan Ung Danielle Hixon Ah Young Yoon Ren X. Sun Heinz-Josef Lenz Jonathan E. Katz Shannon M. Mumenthaler |
| author_facet | Carly Strelez Sujatha Chilakala Kimya Ghaffarian Roy Lau Erin Spiller Nolan Ung Danielle Hixon Ah Young Yoon Ren X. Sun Heinz-Josef Lenz Jonathan E. Katz Shannon M. Mumenthaler |
| author_sort | Carly Strelez |
| collection | DOAJ |
| description | Summary: Colorectal cancer (CRC) progression is a complex process that is not well understood. We describe an in vitro organ-on-chip model that emulates in vivo tissue structure and the tumor microenvironment (TME) to better understand intravasation, an early step in metastasis. The CRC-on-chip incorporates fluid flow and peristalsis-like cyclic stretching and consists of endothelial and epithelial compartments, separated by a porous membrane. On-chip imaging and effluent analyses are used to interrogate CRC progression and the resulting cellular heterogeneity. Mass spectrometry-based metabolite profiles are indicative of a CRC disease state. Tumor cells intravasate from the epithelial channel to the endothelial channel, revealing differences in invasion between aggressive and non-aggressive tumor cells. Tuning the TME by peristalsis-like mechanical forces, the epithelial:endothelial interface, and the addition of fibroblasts influences the invasive capabilities of tumor cells. The CRC-on-chip is a tunable human-relevant model system and a valuable tool to study early invasive events in cancer. |
| first_indexed | 2024-12-16T13:28:34Z |
| format | Article |
| id | doaj.art-caf16ab096014c8ea201b27cc1beccf1 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-12-16T13:28:34Z |
| publishDate | 2021-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-caf16ab096014c8ea201b27cc1beccf12022-12-21T22:30:08ZengElsevieriScience2589-00422021-05-01245102509Human colorectal cancer-on-chip model to study the microenvironmental influence on early metastatic spreadCarly Strelez0Sujatha Chilakala1Kimya Ghaffarian2Roy Lau3Erin Spiller4Nolan Ung5Danielle Hixon6Ah Young Yoon7Ren X. Sun8Heinz-Josef Lenz9Jonathan E. Katz10Shannon M. Mumenthaler11Lawrence J. Ellison Institute for Transformative Medicine, University of Southern California, Los Angeles, CA 90064, USALawrence J. Ellison Institute for Transformative Medicine, University of Southern California, Los Angeles, CA 90064, USALawrence J. Ellison Institute for Transformative Medicine, University of Southern California, Los Angeles, CA 90064, USALawrence J. Ellison Institute for Transformative Medicine, University of Southern California, Los Angeles, CA 90064, USALawrence J. Ellison Institute for Transformative Medicine, University of Southern California, Los Angeles, CA 90064, USALawrence J. Ellison Institute for Transformative Medicine, University of Southern California, Los Angeles, CA 90064, USALawrence J. Ellison Institute for Transformative Medicine, University of Southern California, Los Angeles, CA 90064, USALawrence J. Ellison Institute for Transformative Medicine, University of Southern California, Los Angeles, CA 90064, USALawrence J. Ellison Institute for Transformative Medicine, University of Southern California, Los Angeles, CA 90064, USADivision of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USALawrence J. Ellison Institute for Transformative Medicine, University of Southern California, Los Angeles, CA 90064, USALawrence J. Ellison Institute for Transformative Medicine, University of Southern California, Los Angeles, CA 90064, USA; Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA; Corresponding authorSummary: Colorectal cancer (CRC) progression is a complex process that is not well understood. We describe an in vitro organ-on-chip model that emulates in vivo tissue structure and the tumor microenvironment (TME) to better understand intravasation, an early step in metastasis. The CRC-on-chip incorporates fluid flow and peristalsis-like cyclic stretching and consists of endothelial and epithelial compartments, separated by a porous membrane. On-chip imaging and effluent analyses are used to interrogate CRC progression and the resulting cellular heterogeneity. Mass spectrometry-based metabolite profiles are indicative of a CRC disease state. Tumor cells intravasate from the epithelial channel to the endothelial channel, revealing differences in invasion between aggressive and non-aggressive tumor cells. Tuning the TME by peristalsis-like mechanical forces, the epithelial:endothelial interface, and the addition of fibroblasts influences the invasive capabilities of tumor cells. The CRC-on-chip is a tunable human-relevant model system and a valuable tool to study early invasive events in cancer.http://www.sciencedirect.com/science/article/pii/S2589004221004776Classification DescriptionBioengineeringTissue engineeringCancerBiomedical materials |
| spellingShingle | Carly Strelez Sujatha Chilakala Kimya Ghaffarian Roy Lau Erin Spiller Nolan Ung Danielle Hixon Ah Young Yoon Ren X. Sun Heinz-Josef Lenz Jonathan E. Katz Shannon M. Mumenthaler Human colorectal cancer-on-chip model to study the microenvironmental influence on early metastatic spread iScience Classification Description Bioengineering Tissue engineering Cancer Biomedical materials |
| title | Human colorectal cancer-on-chip model to study the microenvironmental influence on early metastatic spread |
| title_full | Human colorectal cancer-on-chip model to study the microenvironmental influence on early metastatic spread |
| title_fullStr | Human colorectal cancer-on-chip model to study the microenvironmental influence on early metastatic spread |
| title_full_unstemmed | Human colorectal cancer-on-chip model to study the microenvironmental influence on early metastatic spread |
| title_short | Human colorectal cancer-on-chip model to study the microenvironmental influence on early metastatic spread |
| title_sort | human colorectal cancer on chip model to study the microenvironmental influence on early metastatic spread |
| topic | Classification Description Bioengineering Tissue engineering Cancer Biomedical materials |
| url | http://www.sciencedirect.com/science/article/pii/S2589004221004776 |
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