Assessment of stromal SCD-induced drug resistance of PDAC using 3D-printed zPDX model chips
Summary: Lipid metabolism is extensively reprogrammed in pancreatic ductal adenocarcinoma (PDAC). Stearoyl-coenzyme A desaturase (SCD) is a critical lipid regulator that was unexplored in PDAC. Here, we characterized the existence of cancer-associated fibroblasts (CAFs) with high SCD expression, and...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-01-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004222019964 |
| _version_ | 1797946198686957568 |
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| author | Chuntao Wu Beiyuan Hu Lei Wang Xia Wu Haitao Gu Hanguang Dong Jiuliang Yan Zihao Qi Qi Zhang Huan Chen Bo Yu Sheng Hu Yu Qian Shuang Dong Qiang Li Xu Wang Jiang Long |
| author_facet | Chuntao Wu Beiyuan Hu Lei Wang Xia Wu Haitao Gu Hanguang Dong Jiuliang Yan Zihao Qi Qi Zhang Huan Chen Bo Yu Sheng Hu Yu Qian Shuang Dong Qiang Li Xu Wang Jiang Long |
| author_sort | Chuntao Wu |
| collection | DOAJ |
| description | Summary: Lipid metabolism is extensively reprogrammed in pancreatic ductal adenocarcinoma (PDAC). Stearoyl-coenzyme A desaturase (SCD) is a critical lipid regulator that was unexplored in PDAC. Here, we characterized the existence of cancer-associated fibroblasts (CAFs) with high SCD expression, and revealed them as an unfavorable prognostic factor. Therefore, primary CAFs and pancreatic cancer cells were harvested and genetically labeled. The mixture of CAFs and cancer cells were co-injected into scd−/−; prkdc−/−, or hIGF1/INS-expressing zebrafish to generate patient-derived xenograft models (zPDX). The models were aligned in 3D-printed chips for semi-automatic drug administration and high-throughput scanning. The results showed that chaperoning of the SCD-high CAFs significantly improved the drug resistance of pancreatic cancer cells against gemcitabine and cisplatin, while the administration of SCD inhibitors neutralized the protective effect. Our studies revealed the prognostic and therapeutic value of stromal SCD in PDAC, and proposed the application of zPDX model chips for drug testing. |
| first_indexed | 2024-04-10T21:07:05Z |
| format | Article |
| id | doaj.art-f85056a78c374948b37c50eaa615f804 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-10T21:07:05Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-f85056a78c374948b37c50eaa615f8042023-01-22T04:40:33ZengElsevieriScience2589-00422023-01-01261105723Assessment of stromal SCD-induced drug resistance of PDAC using 3D-printed zPDX model chipsChuntao Wu0Beiyuan Hu1Lei Wang2Xia Wu3Haitao Gu4Hanguang Dong5Jiuliang Yan6Zihao Qi7Qi Zhang8Huan Chen9Bo Yu10Sheng Hu11Yu Qian12Shuang Dong13Qiang Li14Xu Wang15Jiang Long16Department of Pancreatic Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China; Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, ChinaDepartment of Pancreatic Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China; Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, ChinaCancer Institute, Fudan University Shanghai Cancer Center, Shanghai 200032, China; School of Basic Medical Sciences, Fudan University, Shanghai 200032, ChinaDepartment of General Practice, Jing’an District Centre Hospital of Shanghai (Huashan Hospital Fudan University Jing’an Branch), Shanghai 200040, ChinaDepartment of Pancreatic Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China; Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, ChinaDepartment of Pancreatic Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China; Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, ChinaDepartment of Pancreatic Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China; Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, ChinaDepartment of Pancreatic Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China; Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, ChinaTranslational Medical Center for Development and Disease, Shanghai Key Laboratory of Birth Defect, Institute of Pediatrics, Children’s Hospital of Fudan University, Shanghai 201102, ChinaNational Human Genetic Resources Sharing Service Platform (2005DKA21300), Fudan University Shanghai Cancer Center, Shanghai 200032, ChinaDepartment of Pharmacy, Tongren Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200336, ChinaDepartment of Thoracic Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430079, ChinaDepartment of Thoracic Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430079, ChinaDepartment of Thoracic Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430079, ChinaTranslational Medical Center for Development and Disease, Shanghai Key Laboratory of Birth Defect, Institute of Pediatrics, Children’s Hospital of Fudan University, Shanghai 201102, China; Corresponding authorCancer Institute, Fudan University Shanghai Cancer Center, Shanghai 200032, China; School of Basic Medical Sciences, Fudan University, Shanghai 200032, China; Corresponding authorDepartment of Pancreatic Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China; Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China; Corresponding authorSummary: Lipid metabolism is extensively reprogrammed in pancreatic ductal adenocarcinoma (PDAC). Stearoyl-coenzyme A desaturase (SCD) is a critical lipid regulator that was unexplored in PDAC. Here, we characterized the existence of cancer-associated fibroblasts (CAFs) with high SCD expression, and revealed them as an unfavorable prognostic factor. Therefore, primary CAFs and pancreatic cancer cells were harvested and genetically labeled. The mixture of CAFs and cancer cells were co-injected into scd−/−; prkdc−/−, or hIGF1/INS-expressing zebrafish to generate patient-derived xenograft models (zPDX). The models were aligned in 3D-printed chips for semi-automatic drug administration and high-throughput scanning. The results showed that chaperoning of the SCD-high CAFs significantly improved the drug resistance of pancreatic cancer cells against gemcitabine and cisplatin, while the administration of SCD inhibitors neutralized the protective effect. Our studies revealed the prognostic and therapeutic value of stromal SCD in PDAC, and proposed the application of zPDX model chips for drug testing.http://www.sciencedirect.com/science/article/pii/S2589004222019964CancerLipidMicroenvironment |
| spellingShingle | Chuntao Wu Beiyuan Hu Lei Wang Xia Wu Haitao Gu Hanguang Dong Jiuliang Yan Zihao Qi Qi Zhang Huan Chen Bo Yu Sheng Hu Yu Qian Shuang Dong Qiang Li Xu Wang Jiang Long Assessment of stromal SCD-induced drug resistance of PDAC using 3D-printed zPDX model chips iScience Cancer Lipid Microenvironment |
| title | Assessment of stromal SCD-induced drug resistance of PDAC using 3D-printed zPDX model chips |
| title_full | Assessment of stromal SCD-induced drug resistance of PDAC using 3D-printed zPDX model chips |
| title_fullStr | Assessment of stromal SCD-induced drug resistance of PDAC using 3D-printed zPDX model chips |
| title_full_unstemmed | Assessment of stromal SCD-induced drug resistance of PDAC using 3D-printed zPDX model chips |
| title_short | Assessment of stromal SCD-induced drug resistance of PDAC using 3D-printed zPDX model chips |
| title_sort | assessment of stromal scd induced drug resistance of pdac using 3d printed zpdx model chips |
| topic | Cancer Lipid Microenvironment |
| url | http://www.sciencedirect.com/science/article/pii/S2589004222019964 |
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