Gupta Priyanka, Bermejo-Rodriguez Camino, Kocher Hemant, Pérez-Mancera Pedro A, Velliou Eirini G
Centre for 3D Models of Health and Disease, Division of Surgery and Interventional Science, University College London, London, W1W 7TY, UK.
Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Ashton Street, Liverpool, L69 3GE, UK.
Adv Biol (Weinh). 2024 Jul;8(7):e2300580. doi: 10.1002/adbi.202300580. Epub 2024 Feb 7.
Pancreatic ductal adenocarcinoma (PDAC) is a challenge for global health with very low survival rate and high therapeutic resistance. Hence, advanced preclinical models for treatment screening are of paramount importance. Herein, chemotherapeutic (gemcitabine) assessment on novel (polyurethane) scaffold-based spatially advanced 3D multicellular PDAC models is carried out. Through comprehensive image-based analysis at the protein level, and expression analysis at the mRNA level, the importance of stromal cells is confirmed, primarily activated stellate cells in the chemoresistance of PDAC cells within the models. Furthermore, it is demonstrated that, in addition to the presence of activated stellate cells, the spatial architecture of the scaffolds, i.e., segregation/compartmentalization of the cancer and stromal zones, affect the cellular evolution and is necessary for the development of chemoresistance. These results highlight that, further to multicellularity, mapping the tumor structure/architecture and zonal complexity in 3D cancer models is important for better mimicry of the in vivo therapeutic response.
胰腺导管腺癌（PDAC）是全球健康面临的一项挑战，其生存率极低且治疗耐药性高。因此，用于治疗筛选的先进临床前模型至关重要。在此，对基于新型（聚氨酯）支架的空间先进3D多细胞PDAC模型进行了化疗（吉西他滨）评估。通过在蛋白质水平上基于图像的综合分析以及在mRNA水平上的表达分析，证实了基质细胞的重要性，主要是活化星状细胞在模型内PDAC细胞化疗耐药性中的作用。此外，研究表明，除了活化星状细胞的存在外，支架的空间结构，即癌症和基质区域的分离/分隔，会影响细胞进化，并且是化疗耐药性发展所必需的。这些结果突出表明，除了多细胞性之外，在3D癌症模型中绘制肿瘤结构/架构和区域复杂性对于更好地模拟体内治疗反应很重要。
