Leaf-vein-inspired multi-organ microfluidic chip for modeling breast cancer CTC organotropism
ObjectiveBreast 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.MethodsW...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2025-05-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2025.1602225/full |
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| author | Liuyin Liu Xiaoli Qu Zhe Wang Cheng Ji Rui Ling Changjiao Yan |
| author_facet | Liuyin Liu Xiaoli Qu Zhe Wang Cheng Ji Rui Ling Changjiao Yan |
| author_sort | Liuyin Liu |
| collection | DOAJ |
| description | ObjectiveBreast 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.MethodsWe 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.ResultsThere 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.ConclusionThis 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. |
| format | Article |
| id | doaj-art-e8e55393529440058a827209632e9b87 |
| institution | OA Journals |
| issn | 2234-943X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj-art-e8e55393529440058a827209632e9b872025-08-20T02:38:19ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-05-011510.3389/fonc.2025.16022251602225Leaf-vein-inspired multi-organ microfluidic chip for modeling breast cancer CTC organotropismLiuyin Liu0Xiaoli Qu1Zhe Wang2Cheng Ji3Rui Ling4Changjiao Yan5Department of Thyroid, Breast, and Vascular Surgery, Xijing Hospital, The Fourth Military Medical University, Xi’an, Shaanxi, ChinaState Key Laboratory for Manufacturing Systems Engineering, Xi’an Jiaotong University, Xi’an, ChinaDepartment of Thyroid, Breast, and Vascular Surgery, Xijing Hospital, The Fourth Military Medical University, Xi’an, Shaanxi, ChinaDepartment of Thyroid, Breast, and Vascular Surgery, Xijing Hospital, The Fourth Military Medical University, Xi’an, Shaanxi, ChinaDepartment of Thyroid, Breast, and Vascular Surgery, Xijing Hospital, The Fourth Military Medical University, Xi’an, Shaanxi, ChinaDepartment of Thyroid, Breast, and Vascular Surgery, Xijing Hospital, The Fourth Military Medical University, Xi’an, Shaanxi, ChinaObjectiveBreast 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.MethodsWe 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.ResultsThere 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.ConclusionThis 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.https://www.frontiersin.org/articles/10.3389/fonc.2025.1602225/fullbreast cancercirculating tumor cellleaf vein architecturemulti-organ microfluidic chiporganotropism |
| spellingShingle | Liuyin Liu Xiaoli Qu Zhe Wang Cheng Ji Rui Ling Changjiao Yan Leaf-vein-inspired multi-organ microfluidic chip for modeling breast cancer CTC organotropism Frontiers in Oncology breast cancer circulating tumor cell leaf vein architecture multi-organ microfluidic chip organotropism |
| title | Leaf-vein-inspired multi-organ microfluidic chip for modeling breast cancer CTC organotropism |
| title_full | Leaf-vein-inspired multi-organ microfluidic chip for modeling breast cancer CTC organotropism |
| title_fullStr | Leaf-vein-inspired multi-organ microfluidic chip for modeling breast cancer CTC organotropism |
| title_full_unstemmed | Leaf-vein-inspired multi-organ microfluidic chip for modeling breast cancer CTC organotropism |
| title_short | Leaf-vein-inspired multi-organ microfluidic chip for modeling breast cancer CTC organotropism |
| title_sort | leaf vein inspired multi organ microfluidic chip for modeling breast cancer ctc organotropism |
| topic | breast cancer circulating tumor cell leaf vein architecture multi-organ microfluidic chip organotropism |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2025.1602225/full |
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