Bioinspired 3D hydrogel scaffold to mimic tumor microenvironment for investigating into the anoikis resistance mechanisms in colorectal cancer
Anoikis resistance constitutes a critical pathophysiological mechanism driving metastatic progression in colorectal cancer. While in vitro models are essential for mechanistic studies, conventional 2D cultures inadequately replicate tumor microenvironment (TME) complexity. In this study, we develope...
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Elsevier
2025-08-01
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| Series: | Materials Today Bio |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590006425006313 |
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| author | Jia Weng Shicheng Li Jiacheng Weng Yan Wang Bincan Deng Mengxian Yao Hongke Hao Xia Huang Lei Gan Bo Chen Xuan Xue Zhigang Chen |
| author_facet | Jia Weng Shicheng Li Jiacheng Weng Yan Wang Bincan Deng Mengxian Yao Hongke Hao Xia Huang Lei Gan Bo Chen Xuan Xue Zhigang Chen |
| author_sort | Jia Weng |
| collection | DOAJ |
| description | Anoikis resistance constitutes a critical pathophysiological mechanism driving metastatic progression in colorectal cancer. While in vitro models are essential for mechanistic studies, conventional 2D cultures inadequately replicate tumor microenvironment (TME) complexity. In this study, we developed a biomimetic composite hydrogel (GHP4a) composed of 4-arm-PEGDA, Gelatin Methacryloyl, and Hyaluronic acid Methacryloyl to establish compact 3D cell spheres that mimic TME. The GHP4a demonstrates superior biocompatibility, suitable mechanical strength at 600–700 Pa, and biomimetic properties that promote cell proliferation and differentiation when co-culturing Caco-2 cells. The cell anchorage and survival for anoikis resistance are enhanced compared to traditional 2D cell incubation due to a well-organized 3D formation akin to the extracellular matrix (ECM). The biomimetic mechanism may be attributed to the fact that the GHP4a promoted the activation of key pro-survival pathways, including FAK and PI3K/Akt signaling, and suppressed caspase-mediated apoptosis. Single-cell RNA sequencing revealed distinct transcriptional profiles within the proliferating T cell population, suggesting a novel regulatory mechanism of T cell-mediated anti-tumor immunity in the TME. Additionally, radiomic analysis identified significant differences in tumor heterogeneity and texture between GHP4a-based 3D cultures and traditional 2D models. These findings established the GHP4a as an effective candidate for the in vitro tumor anoikis resistance model, providing a unique approach for studying anoikis resistance in colorectal cancer and offering a robust tool for the development of advancing cancer diagnosis and therapy strategies. |
| format | Article |
| id | doaj-art-529804e7e89742db9e31a15af01a101d |
| institution | Kabale University |
| issn | 2590-0064 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Materials Today Bio |
| spelling | doaj-art-529804e7e89742db9e31a15af01a101d2025-08-20T03:27:25ZengElsevierMaterials Today Bio2590-00642025-08-013310206110.1016/j.mtbio.2025.102061Bioinspired 3D hydrogel scaffold to mimic tumor microenvironment for investigating into the anoikis resistance mechanisms in colorectal cancerJia Weng0Shicheng Li1Jiacheng Weng2Yan Wang3Bincan Deng4Mengxian Yao5Hongke Hao6Xia Huang7Lei Gan8Bo Chen9Xuan Xue10Zhigang Chen11Department of Chemistry and Materials Science, School of Science, Xi'an Jiaotong-Liverpool University, Suzhou, 215123, Jiangsu Province, China; Department of Chemistry, University of Liverpool, Liverpool, L69 7ZD, UKDepartment of Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, Jiangsu Province, ChinaDepartment of Oncology, Suzhou Xiangcheng People's Hospital, Suzhou, 215131, Jiangsu Province, ChinaInstitute of Materials Science and Devices, School of Materials Science and Engineering Suzhou University of Science and Technology Suzhou, 215009, Jiangsu, ChinaSchool of Mathematics and Physics, Xi'an Jiaotong-Liverpool University, Suzhou, 215123, Jiangsu Province, ChinaDepartment of Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, Jiangsu Province, ChinaDepartment of Biological Sciences and Bioinformatics, School of Science, Xi'an Jiaotong-Liverpool University, Suzhou, 215123, Jiangsu Province, ChinaDepartment of Biological Sciences and Bioinformatics, School of Science, Xi'an Jiaotong-Liverpool University, Suzhou, 215123, Jiangsu Province, ChinaDepartment of Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, Jiangsu Province, China; Corresponding author.Institute of Materials Science and Devices, School of Materials Science and Engineering Suzhou University of Science and Technology Suzhou, 215009, Jiangsu, China; Corresponding author.Department of Chemistry and Materials Science, School of Science, Xi'an Jiaotong-Liverpool University, Suzhou, 215123, Jiangsu Province, China; Department of Chemistry, University of Liverpool, Liverpool, L69 7ZD, UK; Corresponding author. Department of Chemistry, University of Liverpool, Liverpool, L69 7ZD, UK.Department of Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, Jiangsu Province, China; Corresponding author.Anoikis resistance constitutes a critical pathophysiological mechanism driving metastatic progression in colorectal cancer. While in vitro models are essential for mechanistic studies, conventional 2D cultures inadequately replicate tumor microenvironment (TME) complexity. In this study, we developed a biomimetic composite hydrogel (GHP4a) composed of 4-arm-PEGDA, Gelatin Methacryloyl, and Hyaluronic acid Methacryloyl to establish compact 3D cell spheres that mimic TME. The GHP4a demonstrates superior biocompatibility, suitable mechanical strength at 600–700 Pa, and biomimetic properties that promote cell proliferation and differentiation when co-culturing Caco-2 cells. The cell anchorage and survival for anoikis resistance are enhanced compared to traditional 2D cell incubation due to a well-organized 3D formation akin to the extracellular matrix (ECM). The biomimetic mechanism may be attributed to the fact that the GHP4a promoted the activation of key pro-survival pathways, including FAK and PI3K/Akt signaling, and suppressed caspase-mediated apoptosis. Single-cell RNA sequencing revealed distinct transcriptional profiles within the proliferating T cell population, suggesting a novel regulatory mechanism of T cell-mediated anti-tumor immunity in the TME. Additionally, radiomic analysis identified significant differences in tumor heterogeneity and texture between GHP4a-based 3D cultures and traditional 2D models. These findings established the GHP4a as an effective candidate for the in vitro tumor anoikis resistance model, providing a unique approach for studying anoikis resistance in colorectal cancer and offering a robust tool for the development of advancing cancer diagnosis and therapy strategies.http://www.sciencedirect.com/science/article/pii/S2590006425006313Biomimetic hydrogelsAnoikis resistance3D cell scaffoldBioinformatic and radiomics analysisColorectal cancer |
| spellingShingle | Jia Weng Shicheng Li Jiacheng Weng Yan Wang Bincan Deng Mengxian Yao Hongke Hao Xia Huang Lei Gan Bo Chen Xuan Xue Zhigang Chen Bioinspired 3D hydrogel scaffold to mimic tumor microenvironment for investigating into the anoikis resistance mechanisms in colorectal cancer Materials Today Bio Biomimetic hydrogels Anoikis resistance 3D cell scaffold Bioinformatic and radiomics analysis Colorectal cancer |
| title | Bioinspired 3D hydrogel scaffold to mimic tumor microenvironment for investigating into the anoikis resistance mechanisms in colorectal cancer |
| title_full | Bioinspired 3D hydrogel scaffold to mimic tumor microenvironment for investigating into the anoikis resistance mechanisms in colorectal cancer |
| title_fullStr | Bioinspired 3D hydrogel scaffold to mimic tumor microenvironment for investigating into the anoikis resistance mechanisms in colorectal cancer |
| title_full_unstemmed | Bioinspired 3D hydrogel scaffold to mimic tumor microenvironment for investigating into the anoikis resistance mechanisms in colorectal cancer |
| title_short | Bioinspired 3D hydrogel scaffold to mimic tumor microenvironment for investigating into the anoikis resistance mechanisms in colorectal cancer |
| title_sort | bioinspired 3d hydrogel scaffold to mimic tumor microenvironment for investigating into the anoikis resistance mechanisms in colorectal cancer |
| topic | Biomimetic hydrogels Anoikis resistance 3D cell scaffold Bioinformatic and radiomics analysis Colorectal cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2590006425006313 |
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