Matrix-bound EGF promotes malignant phenotypes of breast cancer organoids in the biomimetic ECM of alginate
As multiple malignant phenotypes appear during cancer progression, it is essential to recognize the possible mechanisms from original to metastatic states. However, both two-dimensional monolayer cell culture and in vivo animal models have their inherent limitations, such as lack of proper cell-ECM...
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Elsevier
2025-06-01
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| Series: | Materials Today Bio |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590006425003783 |
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| author | Xue-Yu Chen Meng-Yuan Wang Xin Shu Jun Li Ruizhi Tang Xi-Qiu Liu |
| author_facet | Xue-Yu Chen Meng-Yuan Wang Xin Shu Jun Li Ruizhi Tang Xi-Qiu Liu |
| author_sort | Xue-Yu Chen |
| collection | DOAJ |
| description | As multiple malignant phenotypes appear during cancer progression, it is essential to recognize the possible mechanisms from original to metastatic states. However, both two-dimensional monolayer cell culture and in vivo animal models have their inherent limitations, such as lack of proper cell-ECM interactions and uncontrollable variables. By their heterogeneous simulation of tumor processes, 3D organoids can better recapitulate real tumor characteristics and more realistic responses to distinct factors. Herein, this study was designed to establish in vitro 3D breast cancer organoid models in the recreating tumor-stroma niche by using alginate cryogels to mimic the porous ECM, especially to introduce the controlled release of matrix-bound growth factor EGF (83 % positive in human breast cancers). The matrix-bound EGF in the biomimetic ECM promoted malignant phenotypes of breast cancer organoids in proliferation, migration, epithelial-mesenchymal transition, apoptosis and drug resistance, in accordance with clinical evidence. The multi-omics analyses combined with molecular biological experiments revealed both cytokine-cytokine receptor interaction and ECM-receptor interaction functioned to activate PI3K-AKT pathways, to stimulate tumor-promoting cytokines (eg., IL18, IL33, GDF-15), to promote gene expression of ECM components (eg., FN1) and metabolic enzymes (eg., GOT2), and finally to reprogram breast cancer energy metabolism. This system would represent a new paradigm of cancer progression studies using in vitro 3D organoids in a biomimetic ECM, in order to develop novel therapeutic strategies and evaluate preclinical treatments. |
| format | Article |
| id | doaj-art-d55a182b00fa43ac9b2f6dc2497e6e63 |
| institution | OA Journals |
| issn | 2590-0064 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
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| spelling | doaj-art-d55a182b00fa43ac9b2f6dc2497e6e632025-08-20T01:48:52ZengElsevierMaterials Today Bio2590-00642025-06-013210181810.1016/j.mtbio.2025.101818Matrix-bound EGF promotes malignant phenotypes of breast cancer organoids in the biomimetic ECM of alginateXue-Yu Chen0Meng-Yuan Wang1Xin Shu2Jun Li3Ruizhi Tang4Xi-Qiu Liu5Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, PR ChinaHubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, PR ChinaTongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, PR ChinaHubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, PR ChinaHubei Key Laboratory of Molecular Diagnosis, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430014, PR ChinaHubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, PR China; Corresponding author.As multiple malignant phenotypes appear during cancer progression, it is essential to recognize the possible mechanisms from original to metastatic states. However, both two-dimensional monolayer cell culture and in vivo animal models have their inherent limitations, such as lack of proper cell-ECM interactions and uncontrollable variables. By their heterogeneous simulation of tumor processes, 3D organoids can better recapitulate real tumor characteristics and more realistic responses to distinct factors. Herein, this study was designed to establish in vitro 3D breast cancer organoid models in the recreating tumor-stroma niche by using alginate cryogels to mimic the porous ECM, especially to introduce the controlled release of matrix-bound growth factor EGF (83 % positive in human breast cancers). The matrix-bound EGF in the biomimetic ECM promoted malignant phenotypes of breast cancer organoids in proliferation, migration, epithelial-mesenchymal transition, apoptosis and drug resistance, in accordance with clinical evidence. The multi-omics analyses combined with molecular biological experiments revealed both cytokine-cytokine receptor interaction and ECM-receptor interaction functioned to activate PI3K-AKT pathways, to stimulate tumor-promoting cytokines (eg., IL18, IL33, GDF-15), to promote gene expression of ECM components (eg., FN1) and metabolic enzymes (eg., GOT2), and finally to reprogram breast cancer energy metabolism. This system would represent a new paradigm of cancer progression studies using in vitro 3D organoids in a biomimetic ECM, in order to develop novel therapeutic strategies and evaluate preclinical treatments.http://www.sciencedirect.com/science/article/pii/S2590006425003783Malignant phenotypesCancer organoidsEpidermal growth factorCell-ECM interactionsMulti-omics |
| spellingShingle | Xue-Yu Chen Meng-Yuan Wang Xin Shu Jun Li Ruizhi Tang Xi-Qiu Liu Matrix-bound EGF promotes malignant phenotypes of breast cancer organoids in the biomimetic ECM of alginate Materials Today Bio Malignant phenotypes Cancer organoids Epidermal growth factor Cell-ECM interactions Multi-omics |
| title | Matrix-bound EGF promotes malignant phenotypes of breast cancer organoids in the biomimetic ECM of alginate |
| title_full | Matrix-bound EGF promotes malignant phenotypes of breast cancer organoids in the biomimetic ECM of alginate |
| title_fullStr | Matrix-bound EGF promotes malignant phenotypes of breast cancer organoids in the biomimetic ECM of alginate |
| title_full_unstemmed | Matrix-bound EGF promotes malignant phenotypes of breast cancer organoids in the biomimetic ECM of alginate |
| title_short | Matrix-bound EGF promotes malignant phenotypes of breast cancer organoids in the biomimetic ECM of alginate |
| title_sort | matrix bound egf promotes malignant phenotypes of breast cancer organoids in the biomimetic ecm of alginate |
| topic | Malignant phenotypes Cancer organoids Epidermal growth factor Cell-ECM interactions Multi-omics |
| url | http://www.sciencedirect.com/science/article/pii/S2590006425003783 |
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