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Assessment of stromal SCD-induced drug resistance of PDAC using 3D-printed zPDX model chips

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机构： [1]Department of Pancreatic Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China. [2]Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China. [3]Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai 200032, China. [4]School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. [5]Department of General Practice, Jing'an District Centre Hospital of Shanghai (Huashan Hospital Fudan University Jing'an Branch), Shanghai 200040, China. [6]Translational Medical Center for Development and Disease, Shanghai Key Laboratory of Birth Defect, Institute of Pediatrics, Children's Hospital of Fudan University, Shanghai 201102, China. [7]National Human Genetic Resources Sharing Service Platform (2005DKA21300), Fudan University Shanghai Cancer Center, Shanghai 200032, China. [8]Department of Pharmacy, Tongren Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200336, China. [9]Department of Thoracic Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430079, China.

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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.© 2022 The Authors.

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出版当年[2022]版：

大类 | 2 区综合性期刊

小类 | 2 区综合性期刊

最新[2023]版：

大类 | 2 区综合性期刊

小类 | 2 区综合性期刊

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出版当年[2021]版：

Q1 MULTIDISCIPLINARY SCIENCES

最新[2023]版：

Q1 MULTIDISCIPLINARY SCIENCES

影响因子： 4.6 最新[2023版] 5 最新五年平均 6.107 出版当年[2021版] 6.233 出版当年五年平均 5.458 出版前一年[2020版] 5.8 出版后一年[2022版]

第一作者：

第一作者机构： [1]Department of Pancreatic Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China. [2]Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.

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通讯作者：

通讯机构： [1]Department of Pancreatic Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China. [2]Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China. [3]Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai 200032, China. [4]School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.

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