Studying breast cancer lung metastasis using a multi-compartment microfluidic device with a mimetic tumor-stroma interaction model
Background: Understanding the mechanisms underlying the metastasis of breast cancer cells to the lungs is challenging, and appropriate simulation of the tumor microenvironment with mimetic cancer-stroma crosstalk is essential. β4 integrin is known to contribute to triggering a variety of different s...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-03-01
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| Series: | Translational Oncology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523325000348 |
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| author | Bahareh Zarin Laleh Rafiee Sorosh Abdollahi Maryam Vatani Mohsen Hassani Amir Sanati-Nezhad Shaghayegh Haghjooy Javanmard |
| author_facet | Bahareh Zarin Laleh Rafiee Sorosh Abdollahi Maryam Vatani Mohsen Hassani Amir Sanati-Nezhad Shaghayegh Haghjooy Javanmard |
| author_sort | Bahareh Zarin |
| collection | DOAJ |
| description | Background: Understanding the mechanisms underlying the metastasis of breast cancer cells to the lungs is challenging, and appropriate simulation of the tumor microenvironment with mimetic cancer-stroma crosstalk is essential. β4 integrin is known to contribute to triggering a variety of different signaling cues involved in the malignant phenotype of cancer but its role in organ-specific metastasis needs further study. In this work, a multi-compartment microfluidic tumor model was developed to evaluate cancer cell invasion. Materials and methods: To model the primary tumor microenvironment, breast cancer cells (MCF7) and cancer-associated fibroblasts (CAFs) were co-cultured within the tumor compartment of the microfluidic chip while normal lung fibroblasts (NLFs) were seeded in a different compartment, as the secondary tumor site, separated from the tumor compartment via a Matrigel™ layer resembling the extracellular matrix. Results: The cytotoxic effect of β4 integrin blockade on cancer cells gradually increased after 48 and 72 h of co-culture. Invasion of breast cancer cells in both single and coculture models was characterized in response to β4 integrin blockade. The invasion rate and gap closure of MCF7/CAF_NLF was significantly higher than MCF7_NLF (P < 0.0001). β4 integrin inhibition reduced the rate of gap closure and invasion of both (P < 0.0001). Conclusions: Biomimetic microfluidic-based tumor models hold promise for studying cancer metastasis mechanisms. Precise manipulation, simulation, and analysis of the cancer microenvironment are made possible by microfluidics. |
| format | Article |
| id | doaj-art-f24d70f47b3441b7aaccba74a3f87c5d |
| institution | Kabale University |
| issn | 1936-5233 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj-art-f24d70f47b3441b7aaccba74a3f87c5d2025-02-05T04:31:39ZengElsevierTranslational Oncology1936-52332025-03-0153102303Studying breast cancer lung metastasis using a multi-compartment microfluidic device with a mimetic tumor-stroma interaction modelBahareh Zarin0Laleh Rafiee1Sorosh Abdollahi2Maryam Vatani3Mohsen Hassani4Amir Sanati-Nezhad5Shaghayegh Haghjooy Javanmard6Department of Physiology, Applied Physiology Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran; BioMEMS and Bioinspired Microfluidic Laboratory, Department of Biomedical Engineering, University of Calgary, Calgary, Alberta, CanadaDepartment of Physiology, Applied Physiology Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, IranBioMEMS and Bioinspired Microfluidic Laboratory, Department of Biomedical Engineering, University of Calgary, Calgary, Alberta, Canada; Biomedical Engineering Program, University of Calgary, Calgary, Alberta, CanadaBioMEMS and Bioinspired Microfluidic Laboratory, Department of Biomedical Engineering, University of Calgary, Calgary, Alberta, Canada; Biomedical Engineering Program, University of Calgary, Calgary, Alberta, CanadaBioMEMS and Bioinspired Microfluidic Laboratory, Department of Biomedical Engineering, University of Calgary, Calgary, Alberta, Canada; Department of Mechanical and Manufacturing Engineering, University of Calgary, Calgary, Alberta, CanadaBioMEMS and Bioinspired Microfluidic Laboratory, Department of Biomedical Engineering, University of Calgary, Calgary, Alberta, Canada; Biomedical Engineering Program, University of Calgary, Calgary, Alberta, Canada; Department of Mechanical and Manufacturing Engineering, University of Calgary, Calgary, Alberta, Canada; Corresponding authors.Metabolomics and Genomics Research Center, Cellular and Molecular Institute, Endocrinology and Metabolism Research Institute, Tehran University of Medical Sciences, Tehran, Iran; Corresponding authors.Background: Understanding the mechanisms underlying the metastasis of breast cancer cells to the lungs is challenging, and appropriate simulation of the tumor microenvironment with mimetic cancer-stroma crosstalk is essential. β4 integrin is known to contribute to triggering a variety of different signaling cues involved in the malignant phenotype of cancer but its role in organ-specific metastasis needs further study. In this work, a multi-compartment microfluidic tumor model was developed to evaluate cancer cell invasion. Materials and methods: To model the primary tumor microenvironment, breast cancer cells (MCF7) and cancer-associated fibroblasts (CAFs) were co-cultured within the tumor compartment of the microfluidic chip while normal lung fibroblasts (NLFs) were seeded in a different compartment, as the secondary tumor site, separated from the tumor compartment via a Matrigel™ layer resembling the extracellular matrix. Results: The cytotoxic effect of β4 integrin blockade on cancer cells gradually increased after 48 and 72 h of co-culture. Invasion of breast cancer cells in both single and coculture models was characterized in response to β4 integrin blockade. The invasion rate and gap closure of MCF7/CAF_NLF was significantly higher than MCF7_NLF (P < 0.0001). β4 integrin inhibition reduced the rate of gap closure and invasion of both (P < 0.0001). Conclusions: Biomimetic microfluidic-based tumor models hold promise for studying cancer metastasis mechanisms. Precise manipulation, simulation, and analysis of the cancer microenvironment are made possible by microfluidics.http://www.sciencedirect.com/science/article/pii/S1936523325000348Breast cancerLung metastasisMicrofluidicsβ4 integrinTumor microenvironment |
| spellingShingle | Bahareh Zarin Laleh Rafiee Sorosh Abdollahi Maryam Vatani Mohsen Hassani Amir Sanati-Nezhad Shaghayegh Haghjooy Javanmard Studying breast cancer lung metastasis using a multi-compartment microfluidic device with a mimetic tumor-stroma interaction model Translational Oncology Breast cancer Lung metastasis Microfluidics β4 integrin Tumor microenvironment |
| title | Studying breast cancer lung metastasis using a multi-compartment microfluidic device with a mimetic tumor-stroma interaction model |
| title_full | Studying breast cancer lung metastasis using a multi-compartment microfluidic device with a mimetic tumor-stroma interaction model |
| title_fullStr | Studying breast cancer lung metastasis using a multi-compartment microfluidic device with a mimetic tumor-stroma interaction model |
| title_full_unstemmed | Studying breast cancer lung metastasis using a multi-compartment microfluidic device with a mimetic tumor-stroma interaction model |
| title_short | Studying breast cancer lung metastasis using a multi-compartment microfluidic device with a mimetic tumor-stroma interaction model |
| title_sort | studying breast cancer lung metastasis using a multi compartment microfluidic device with a mimetic tumor stroma interaction model |
| topic | Breast cancer Lung metastasis Microfluidics β4 integrin Tumor microenvironment |
| url | http://www.sciencedirect.com/science/article/pii/S1936523325000348 |
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