Affiliation:
1. The Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen 518000, China
2. Department of Biomedical Engineering, The Hong Kong Polytechnic University, Hong Kong 999077, China
Abstract
Tumor cells metastasize from a primary lesion to distant organs mainly through hematogenous dissemination, in which tumor cell re-adhesion to the endothelium is essential before extravasating into the target site. We thus hypothesize that tumor cells with the ability to adhere to the endothelium of a specific organ exhibit enhanced metastatic tropism to this target organ. This study tested this hypothesis and developed an in vitro model to mimic the adhesion between tumor cells and brain endothelium under fluid shear stress, which selected a subpopulation of tumor cells with enhanced adhesion strength. The selected cells up-regulated the genes related to brain metastasis and exhibited an enhanced ability to transmigrate through the blood–brain barrier. In the soft microenvironments that mimicked brain tissue, these cells had elevated adhesion and survival ability. Further, tumor cells selected by brain endothelium adhesion expressed higher levels of MUC1, VCAM1, and VLA-4, which were relevant to breast cancer brain metastasis. In summary, this study provides the first piece of evidence to support that the adhesion of circulating tumor cells to the brain endothelium selects the cells with enhanced brain metastasis potential.
Funder
National Natural Science Foundation of China
Shenzhen Science and Technology Innovation Commission
General Research Fund of Hong Kong Research Grant Council
Health and Medical Research Fund
Germany/Hong Kong Joint Research Scheme
Hong Kong Polytechnic University Shenzhen Research Institute
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
Reference64 articles.
1. Tumor Metastasis: Molecular Insights and Evolving Paradigms;Valastyan;Cell,2011
2. EMT, MET, Plasticity, and Tumor Metastasis;Bakir;Trends Cell Biol.,2020
3. Mechanical Adaptability of Tumor Cells in Metastasis;Gensbittel;Dev. Cell,2021
4. Metastasis as an evolutionary process;Turajlic;Science,2016
5. Hemodynamic Forces Tune the Arrest, Adhesion, and Extravasation of Circulating Tumor Cells;Follain;Dev. Cell,2018
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