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Intravasation-On-µDevice (INVADE): Engineering Dynamic Vascular Interfaces to Study Cancer Cell Intravasation
Fengtao Jiang1, Yingqi Zhang1, Guocheng Fang2
1School of Biomedical Engineering, Faculty of Engineering, The University of Sydney, Darlington, NSW, 2008, Australia.
A new microfluidic device models cancer cell intravasation, revealing distinct invasion mechanisms and a novel epithelial-mesenchymal transition switch. Endothelial cells actively suppress cancer cell invasiveness, highlighting complex interactions during metastasis.
Area of Science:
- Biomedical Engineering
- Cancer Biology
- Microfluidics
Background:
- Cancer metastasis involves cancer cells entering blood vessels (intravasation) via endothelial barriers.
- Current models lack the physiological relevance to fully understand intravasation mechanisms.
Purpose of the Study:
- To develop a biomimetic microfluidic platform for high-throughput analysis of cancer cell intravasation.
- To uncover distinct intravasation mechanisms and cellular interactions.
Main Methods:
- Development of the INVADE (Intravasation-on-µDevice) microfluidic platform with 23 parallel niche chambers and an endothelialized channel.
- Real-time visualization and analysis of cancer cell behavior during intravasation.
- Quantitative analysis of molecular markers like Vimentin and EpCAM.
Main Results:
- Distinct intravasation modes observed: collective invasion (MCF-7) and interactive mode (MDA-MB-231).
- Discovery of a novel epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) switch during intravasation.
- Endothelial cells significantly suppress cancer cell mesenchymal properties (4.6-fold Vimentin reduction).
- Aggressive cancer cells induce intercellular adhesion molecule-1 (ICAM-1) upregulation in endothelium.
Conclusions:
- The INVADE platform provides a physiologically relevant model for studying cancer cell intravasation.
- Identified a dynamic EMT/MET switch and direct endothelial suppression of cancer cell invasiveness.
- Elucidated complex, bilateral interactions between cancer cells and endothelial cells during metastasis.
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