Spennati, G., Horowitz, L. F., McGarry, D. J., Rudzka, D. A., Armstrong, G., Olson, M. F., Folch, A. and Yin, H. (2021) Organotypic platform for studying cancer cell metastasis. Experimental Cell Research, 401(2), 112527. (doi: 10.1016/j.yexcr.2021.112527) (PMID:33675807)
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Abstract
Metastasis is the leading cause of mortality in cancer patients. To migrate to distant sites, cancer cells would need to adapt their behaviour in response to different tissue environments. Thus, it is essential to study this process in models that can closely replicate the tumour microenvironment. Here, we evaluate the use of organotypic liver and brain slices to study cancer metastasis. Morphological and viability parameters of the slices were monitored daily over 3 days in culture to assess their stability as a realistic 3D tissue platform for in vitro metastatic assays. Using these slices, we evaluated the invasion of MDA-MB-231 breast cancer cells and of a subpopulation that was selected for increased motility. We show that the more aggressive invasion of the selected cells likely resulted not only from their lower stiffness, but also from their lower adhesion to the surrounding tissue. Different invasion patterns in the brain and liver slices were observed for both subpopulations. Cells migrated faster in the brain slices (with an amoeboid-like mode) compared to in the liver slices (where they migrated with mesenchymal or collective migration-like modes). Inhibition of the Ras/MAPK/ERK pathway increased cell stiffness and adhesion forces, which resulted in reduced invasiveness. These results illustrate the potential for organotypic tissue slices to more closely mimic in vivo conditions during cancer cell metastasis than most in vitro models.
Item Type: | Articles |
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Additional Information: | Giulia Spennati thanks EPSRC for her studentship and Vest Scholarship for her visit to the University of Washington. We thank financial support from EPSRC SofTMech (EP/N014642/1), the National Cancer Institute R01 CA181445-01A1, Cancer Research UK (A10419 & A17196 to the CRUK Beatson Institute; A18276 to the Olson lab), the Canadian Institutes of Health Research (PJT-169125 to Olson), Natural Sciences and Engineering Research Council of Canada (RGPIN-2020-05388) and Canada Research Chairs Program (950-231665). |
Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Yin, Professor Huabing and Rudzka, Dr Dominika |
Authors: | Spennati, G., Horowitz, L. F., McGarry, D. J., Rudzka, D. A., Armstrong, G., Olson, M. F., Folch, A., and Yin, H. |
College/School: | College of Medical Veterinary and Life Sciences > School of Cancer Sciences College of Science and Engineering > School of Engineering > Biomedical Engineering |
Journal Name: | Experimental Cell Research |
Publisher: | Elsevier |
ISSN: | 0014-4827 |
ISSN (Online): | 1090-2422 |
Published Online: | 04 March 2021 |
Copyright Holders: | Copyright © 2021 Elsevier |
First Published: | First published in Experimental Cell Research 401(2): 112527 |
Publisher Policy: | Reproduced in accordance with the copyright policy of the publisher |
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