Organotypic platform for studying cancer cell metastasis

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
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 > Institute 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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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
172141EPSRC Centre for Multiscale soft tissue mechanics with application to heart & cancerRaymond OgdenEngineering and Physical Sciences Research Council (EPSRC)EP/N014642/1M&S - Mathematics