PUBLICATION
Assessment of stromal SCD-induced drug resistance of PDAC using 3D-printed zPDX model chips
- Authors
- Wu, C., Hu, B., Wang, L., Wu, X., Gu, H., Dong, H., Yan, J., Qi, Z., Zhang, Q., Chen, H., Yu, B., Hu, S., Qian, Y., Dong, S., Li, Q., Wang, X., Long, J.
- ID
- ZDB-PUB-230103-2
- Date
- 2022
- Source
- iScience 26: 105723105723 (Journal)
- Registered Authors
- Li, Qiang, Wang, Xu
- Keywords
- Cancer, Lipid, Microenvironment
- MeSH Terms
- none
- PubMed
- 36590169 Full text @ iScience
Citation
Wu, C., Hu, B., Wang, L., Wu, X., Gu, H., Dong, H., Yan, J., Qi, Z., Zhang, Q., Chen, H., Yu, B., Hu, S., Qian, Y., Dong, S., Li, Q., Wang, X., Long, J. (2022) Assessment of stromal SCD-induced drug resistance of PDAC using 3D-printed zPDX model chips. iScience. 26:105723105723.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping