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Updated: Jun 15, 2025
Author Spotlight: Creating Human Vascularized Micro-Tumors as Models for Translational Cancer Research
Published on: September 15, 2023
Leaf-vein-inspired multi-organ microfluidic chip for modeling breast cancer CTC organotropism
Liuyin Liu1, Xiaoli Qu2, Zhe Wang1
1Department of Thyroid, Breast, and Vascular Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China.
Objective:
Breast cancer is characterized by a high tendency for organ-specific metastasis. This study aims to develop a multi-organ metastasis model for circulating tumor cells (CTCs) of breast cancer to explore their organotropism in common target organs, including the liver, bone, and lung.
Methods:
We fabricated a biomimetic microfluidic organ-on-a-chip inspired by leaf veins. In this system, three-dimensional cultures of human hepatocyte LO2 cells, human bone marrow-derived mesenchymal stem cells, and human fetal lung fibroblast 1 cells were established in separate chambers to mimic liver, bone, and lung microenvironments, respectively. Then, various breast cancer subtypes (MCF-7, SKBR3, MDA-MB-231) were perfused through the system. We quantified their invasive cell numbers and organ-specific localization in each organ. Further, MDA-MB-231 cells overexpressing metastasis-related genes (CXCR4, claudin-2, Linc-ZNF469-3) were tested. Additionally, the integration of tumor organoids with microfluidic chips was employed to evaluate the predictive capacity of this model for patient-specific metastatic patterns.
Results:
There are significant differences in the number of invasive cells and organ-specific localization among different breast cancer subtypes in each organ. MCF-7 cells show the highest invasion and most prominent localization in bone; SKBR3 cells in liver and lung. MDA-MB-231 cells have no obvious difference in organotropism among the three organs, but their invasive numbers are higher than those of MCF-7 cells. CXCR4-OE, claudin-2-OE, and Linc-ZNF469-3-OE MDA-MB-231 cells demonstrate the highest invasion and most prominent localization in bone, liver, and lung respectively. Organoid cells derived from a breast cancer patient with pulmonary metastasis at initial diagnosis, when perfused into the system, selectively invaded the lung organ, but did not invade the liver, bone, or control pores.
Conclusion:
This leaf-vein-inspired multi-organ microfluidic chip demonstrates significant application value for studying breast cancer CTC organotropism and serves as a powerful predictive tool for early warning of high-risk organ metastasis.
Insights
This study developed a leaf-vein-inspired microfluidic chip to model breast cancer metastasis to the liver, bone, and lung. The chip accurately predicts organotropism and patient-specific metastatic patterns, serving as an early warning tool.
Area of Science:
- Oncology
- Biomedical Engineering
- Cell Biology
Background:
- Breast cancer exhibits a high propensity for organ-specific metastasis.
- Understanding the organotropism of circulating tumor cells (CTCs) is crucial for predicting metastatic patterns.
Purpose of the Study:
- To develop a multi-organ metastasis model for breast cancer CTCs.
- To explore the organotropism of different breast cancer subtypes in liver, bone, and lung microenvironments.
- To evaluate the predictive capacity of the model for patient-specific metastatic patterns.
Main Methods:
- Fabrication of a biomimetic, leaf-vein-inspired microfluidic organ-on-a-chip.
- Establishment of 3D cultures mimicking liver, bone, and lung microenvironments.
- Perfusion of various breast cancer cell lines (MCF-7, SKBR3, MDA-MB-231) and patient-derived organoids through the chip.
- Quantification of invasive cell numbers and organ-specific localization.
- Assessment of metastasis-related gene-overexpressing cells (CXCR4, claudin-2, Linc-ZNF469-3).
Main Results:
- Significant differences in invasion and localization were observed among breast cancer subtypes across different organs.
- MCF-7 cells showed highest bone invasion; SKBR3 cells favored liver and lung.
- MDA-MB-231 cells exhibited higher invasion overall, with specific gene overexpression leading to preferential organ colonization (bone, liver, lung).
- Patient-derived organoids selectively invaded the lung, mirroring clinical pulmonary metastasis.
Conclusions:
- The leaf-vein-inspired multi-organ microfluidic chip effectively models breast cancer CTC organotropism.
- The system serves as a valuable predictive tool for early detection of high-risk organ metastasis.
- This model holds significant potential for personalized medicine and understanding metastasis.
