Lung cancer intravasation-on-a-chip: Visualization and machine learning-assisted automatic quantification
Bioactive Materials, vol. 51, pp. 858–875
Abstract
microphysiological model of EMT-driven lung cancer intravasation-on-a-chip was developed and coupled with machine learning (ML)-assisted automatic identification and quantification of intravasation events. A robust EMT-inducing cocktail (EMT-IC) was formulated by augmenting macrophage-conditioned medium with transforming growth factor-β1. When introduced into microvascular networks (MVNs) in microfluidic devices, EMT-IC did not affect MVN stability and physiologically relevant barrier functions. To model lung cancer intravasation on-a-chip, EMT-IC was supplemented into co-cultures of lung tumor micromasses and MVNs. Wihin 24 h of exposure, EMT-IC facilitated the insertion of membrane protrusions of migratory A549 cells into microvascular structures, followed by successful intravasation. EMT-IC reduced key basement membrane and vascular junction proteins - laminin and VE-Cadherin - rendering vessel walls more permissive to intravasating cells. ML-assisted vessel segmentation combined with co-localization analysis to detect intravasation events confirmed that EMT induction significantly increased the number of intravasation events. Introducing metastatic (NCI-H1975) and non-metastatic (BEAS-2B) cell lines demonstrated that both, baseline intravasation potential and responsiveness to EMT-IC, are reflected in the metastatic predisposition of lung cancer cell lines, highlighting the model's universal applicability and cell-specific sensitivity. The reproducible detection of intravasation events in the established model provides a physiologically relevant platform to study processes of cancer metastasis with high spatio-temporal resolution and short timeframe. This approach holds promise for improved drug development and informed personalized patient treatment plans.
Authors 8
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Chinese University of Hong Kong
Affiliation as printed
Center for Neuromusculoskeletal Restorative Medicine (CNRM), Hong Kong Science Park, Shatin, New Territories, Hong Kong SAR, China
Institute for Tissue Engineering and Regenerative Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
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Chinese University of Hong Kong
Affiliation as printed
Center for Neuromusculoskeletal Restorative Medicine (CNRM), Hong Kong Science Park, Shatin, New Territories, Hong Kong SAR, China
Institute for Tissue Engineering and Regenerative Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
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Chinese University of Hong Kong
Affiliation as printed
Center for Neuromusculoskeletal Restorative Medicine (CNRM), Hong Kong Science Park, Shatin, New Territories, Hong Kong SAR, China
Institute for Tissue Engineering and Regenerative Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
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Chinese University of Hong Kong
Affiliation as printed
Center for Neuromusculoskeletal Restorative Medicine (CNRM), Hong Kong Science Park, Shatin, New Territories, Hong Kong SAR, China
Institute for Tissue Engineering and Regenerative Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
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Caroline Kniebs Aachen Department of Biohybrid and Medical Textiles (BioTex) AME-Institute of Applied Medical Engineering
Chinese University of Hong Kong · RWTH Aachen University
Affiliation as printed
Department of Biohybrid and Medical Textiles (BioTex), AME - Institute of Applied Medical Engineering, Helmholtz Institute, RWTH Aachen University, Aachen, Germany
Institute for Tissue Engineering and Regenerative Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
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Hong Kong Polytechnic University · Chinese University of Hong Kong
Affiliation as printed
Center for Neuromusculoskeletal Restorative Medicine (CNRM), Hong Kong Science Park, Shatin, New Territories, Hong Kong SAR, China
Department of Biomedical Engineering, The Hong Kong Polytechnic University, Hong Kong SAR, China
Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
Institute for Tissue Engineering and Regenerative Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
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Chinese University of Hong Kong
Affiliation as printed
Center for Neuromusculoskeletal Restorative Medicine (CNRM), Hong Kong Science Park, Shatin, New Territories, Hong Kong SAR, China
Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
Institute for Tissue Engineering and Regenerative Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
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Anna Maria Blocki corresponding
Chinese University of Hong Kong
Affiliation as printed
Center for Neuromusculoskeletal Restorative Medicine (CNRM), Hong Kong Science Park, Shatin, New Territories, Hong Kong SAR, China
Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
Institute for Tissue Engineering and Regenerative Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
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