Adjustable extracellular matrix rigidity tumor model for studying stiffness dependent pancreatic ductal adenocarcinomas progression and tumor immunosuppression
Abstract Pancreatic ductal adenocarcinomas (PDAC) is one of the stiffest malignancies with strong solid stresses. Increasing stiffness could alter cellular behavior and trigger internal signaling pathways and is strongly associated with a poor prognosis in PDAC. So far, there has been no report on o...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-05-01
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| Series: | Bioengineering & Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/btm2.10518 |
| _version_ | 1827946059459985408 |
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| author | Haoxiang Zhang Jiaoshun Chen Xiaoqing Hu Jianwei Bai Tao Yin |
| author_facet | Haoxiang Zhang Jiaoshun Chen Xiaoqing Hu Jianwei Bai Tao Yin |
| author_sort | Haoxiang Zhang |
| collection | DOAJ |
| description | Abstract Pancreatic ductal adenocarcinomas (PDAC) is one of the stiffest malignancies with strong solid stresses. Increasing stiffness could alter cellular behavior and trigger internal signaling pathways and is strongly associated with a poor prognosis in PDAC. So far, there has been no report on of an experimental model that can rapidly construct and stably maintain a stiffness gradient dimension in both vitro and in vivo. In this study, a gelatin methacryloyl (GelMA)‐based hydrogel was designed for in vitro and in vivo PDAC experiments. The GelMA‐based hydrogel has porous, adjustable mechanical properties and excellent in vitro and in vivo biocompatibility. The GelMA‐based in vitro 3D culture method can effectively form a gradient and stable extracellular matrix stiffness, affecting cell morphology, cytoskeleton remodeling, and malignant biological behaviors such as proliferation and metastasis. This model is suitable for in vivo studies with long‐term maintenance of matrix stiffness and no significant toxicity. High matrix stiffness can significantly promote PDAC progression and tumor immunosuppression. This novel adaptive extracellular matrix rigidity tumor model is an excellent candidate for further development as an in vitro and in vivo biomechanical study model of PDAC or other tumors with strong solid stresses. |
| first_indexed | 2024-03-13T10:53:22Z |
| format | Article |
| id | doaj.art-74ffbf0006764b93a09b0ae3e14e8452 |
| institution | Directory Open Access Journal |
| issn | 2380-6761 |
| language | English |
| last_indexed | 2024-03-13T10:53:22Z |
| publishDate | 2023-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Bioengineering & Translational Medicine |
| spelling | doaj.art-74ffbf0006764b93a09b0ae3e14e84522023-05-17T07:33:11ZengWileyBioengineering & Translational Medicine2380-67612023-05-0183n/an/a10.1002/btm2.10518Adjustable extracellular matrix rigidity tumor model for studying stiffness dependent pancreatic ductal adenocarcinomas progression and tumor immunosuppressionHaoxiang Zhang0Jiaoshun Chen1Xiaoqing Hu2Jianwei Bai3Tao Yin4Department of Pancreatic Surgery, Union Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 ChinaDepartment of Pancreatic Surgery, Union Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 ChinaDepartment of Ultrasound Medicine, Union Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 ChinaDepartment of Pancreatic Surgery, Union Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 ChinaDepartment of Pancreatic Surgery, Union Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 ChinaAbstract Pancreatic ductal adenocarcinomas (PDAC) is one of the stiffest malignancies with strong solid stresses. Increasing stiffness could alter cellular behavior and trigger internal signaling pathways and is strongly associated with a poor prognosis in PDAC. So far, there has been no report on of an experimental model that can rapidly construct and stably maintain a stiffness gradient dimension in both vitro and in vivo. In this study, a gelatin methacryloyl (GelMA)‐based hydrogel was designed for in vitro and in vivo PDAC experiments. The GelMA‐based hydrogel has porous, adjustable mechanical properties and excellent in vitro and in vivo biocompatibility. The GelMA‐based in vitro 3D culture method can effectively form a gradient and stable extracellular matrix stiffness, affecting cell morphology, cytoskeleton remodeling, and malignant biological behaviors such as proliferation and metastasis. This model is suitable for in vivo studies with long‐term maintenance of matrix stiffness and no significant toxicity. High matrix stiffness can significantly promote PDAC progression and tumor immunosuppression. This novel adaptive extracellular matrix rigidity tumor model is an excellent candidate for further development as an in vitro and in vivo biomechanical study model of PDAC or other tumors with strong solid stresses.https://doi.org/10.1002/btm2.10518extracellular matrix rigiditygelatin methacryloylhydrogelspancreatic cancertumor immunosuppression |
| spellingShingle | Haoxiang Zhang Jiaoshun Chen Xiaoqing Hu Jianwei Bai Tao Yin Adjustable extracellular matrix rigidity tumor model for studying stiffness dependent pancreatic ductal adenocarcinomas progression and tumor immunosuppression Bioengineering & Translational Medicine extracellular matrix rigidity gelatin methacryloyl hydrogels pancreatic cancer tumor immunosuppression |
| title | Adjustable extracellular matrix rigidity tumor model for studying stiffness dependent pancreatic ductal adenocarcinomas progression and tumor immunosuppression |
| title_full | Adjustable extracellular matrix rigidity tumor model for studying stiffness dependent pancreatic ductal adenocarcinomas progression and tumor immunosuppression |
| title_fullStr | Adjustable extracellular matrix rigidity tumor model for studying stiffness dependent pancreatic ductal adenocarcinomas progression and tumor immunosuppression |
| title_full_unstemmed | Adjustable extracellular matrix rigidity tumor model for studying stiffness dependent pancreatic ductal adenocarcinomas progression and tumor immunosuppression |
| title_short | Adjustable extracellular matrix rigidity tumor model for studying stiffness dependent pancreatic ductal adenocarcinomas progression and tumor immunosuppression |
| title_sort | adjustable extracellular matrix rigidity tumor model for studying stiffness dependent pancreatic ductal adenocarcinomas progression and tumor immunosuppression |
| topic | extracellular matrix rigidity gelatin methacryloyl hydrogels pancreatic cancer tumor immunosuppression |
| url | https://doi.org/10.1002/btm2.10518 |
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