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Three-Dimensional Human Liver-Chip Emulating Premetastatic Niche Formation by Breast Cancer-Derived Extracellular
Junyoung Kim1,2, Chaeeun Lee1,2, Inun Kim2
1Department of Biomedical Engineering, School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of Korea.
ACS Nano
|September 4, 2020
Summary
Breast cancer extracellular vesicles (EVs) promote liver metastasis by activating liver cells and increasing cancer cell adhesion. A 3D liver-chip model reveals how EVs create a premetastatic niche, offering insights into therapeutic strategies.
Area of Science:
- Oncology
- Cell Biology
- Biomedical Engineering
Background:
- Liver metastasis is a frequent and lethal complication of breast cancer.
- Tumor microenvironment interactions are crucial but poorly understood in metastasis.
- Extracellular vesicles (EVs) play a role in premetastatic niche formation.
Purpose of the Study:
- To investigate the role of breast cancer-derived EVs in establishing a premetastatic liver niche.
- To understand the mechanism by which EVs facilitate breast cancer cell adhesion to the liver.
Main Methods:
- Development of a 3D microfluidic human liver-on-a-chip (liver-chip) model.
- Analysis of breast cancer-derived EVs and their effects on liver sinusoidal endothelial cells (LSECs).
- Comparison of EVs from healthy donors, nonmetastatic TNBC patients, and metastatic TNBC patients.
Main Results:
- Breast cancer EVs activate LSECs, inducing endothelial-mesenchymal transition and barrier disruption.
- EV-derived TGFβ1 upregulates fibronectin on LSECs, enhancing breast cancer cell adhesion.
- EVs from metastatic TNBC patients show higher TGFβ1 and promote greater cancer cell adhesion.
Conclusions:
- Breast cancer EVs contribute to liver metastasis by modifying the liver microenvironment.
- TGFβ1 in EVs is a key mediator of cancer cell adhesion to the liver.
- The 3D liver-chip is a valuable platform for studying liver metastasis and developing therapies.
