3D models of human pancreatic cancer recapitulate tumour biology
2021
Queen Mary University of London, London, United Kingdom(1)
Shanghai Jiao Tong University School of Medicine, Shanghai, China(2)
Shanghai Jiao Tong University School of Medicine, Shanghai, China(2)
Tailored ex vivo models may be particularly useful for the treatment of pancreatic ductal adenocarcinoma (PDAC), as treatment failure in this tumor type has been attributed to the high content of cancer stem cells (CSCs) and the high density of stromal cells and extracellular matrix (ECM). To date, these features could only be partially reproduced ex vivo using organoid and spheroid cultures. Here, the researchers develop a more comprehensive and customizable ex vivo model of PDAC based on 3D co-assembly of peptide amphiphiles (PAs) with custom ECM components (PA-ECM). These cultures maintain patient-specific transcriptional profiles and exhibit CSC functionality, including strong in vivo tumorigenicity. Custom modification of the system can control niche-dependent phenotypes such as epithelial-to-mesenchymal transition and matrix deposition. Proteomic analysis of these cultures shows a better recapitulation of the matrisome compared to organoids. In addition, patient-specific in vivo drug responses are better reproduced in the composite cultures than in other models. These results support the use of tunable self-assembling platforms in cancer research and pave the way for future precision medicine approaches.
Bioengineered 3D models of human pancreatic cancer recapitulate in vivo tumour biology
Alvaro Mata(1), Daniela Loessner(1), Christopher Heeschen(2)
Added on: 10-20-2021
[1] https://www.nature.com/articles/s41467-021-25921-9?emci=9dd66ae8-d22d-ec11-981f-c896653b9208&emdi=803aa719-2430-ec11-981f-c896653b9208&ceid=2015591#citeas
