Details

Autor(en) / Beteiligte

• Zhao, Yuanyuan
• Zhang, Bing
• Ma, Yiming
• Zhao, Fuqiang
• Chen, Jianan
• Wang, Bingzhi
• Jin, Hua
• Zhou, Fulai
• Guan, Jiawei
• Zhao, Qian
• Wang, Hongying
• Liu, Qian
• Zhao, Fangqing
• Wang, Xia

Titel

Colorectal Cancer Patient‐Derived 2D and 3D Models Efficiently Recapitulate Inter‐ and Intratumoral Heterogeneity

Ist Teil von

• Advanced science, 2022-08, Vol.9 (22), p.e2201539-n/a

Ort / Verlag

Germany: John Wiley & Sons, Inc

Erscheinungsjahr

2022

Link zum Volltext

Quelle

Wiley Online Library Journals Frontfile Complete

Beschreibungen/Notizen

• Pre‐existing drug resistance and tumorigenicity of cancer cells are highly correlated with therapeutic failure and tumor growth. However, current cancer models are limited in their application to the study of intratumor functional heterogeneity in personalized oncology. Here, an innovative two‐dimensional (2D) and three‐dimensional (3D) model for patient‐derived cancer cells (PDCCs) and air–liquid interface (ALI) organotypic culture is established from colorectal cancer (CRC). The PDCCs recapitulate the genomic landscape of their parental tumors with high efficiency, high proliferation rate, and long‐term stability, while corresponding ALI organotypic cultures retain histological architecture of their original tumors. Interestingly, both 2D and 3D models maintain the transcriptomic profile of the corresponding primary tumors and display the same trend in response to 5‐Fluoruracil, regardless of their difference in gene expression profiles. Furthermore, single‐cell‐derived clones() are efficiently established and pre‐existing drug‐resistant clones and highly tumorigenic clones within individual CRC tumors are identified. It is found that tumorigenic cancer cells do not necessarily possess the stem cells characteristics in gene expression. This study provides valuable platform and resource for exploring the molecular mechanisms underlying the pre‐existing drug resistance and tumorigenicity in cancer cells, as well as for developing therapeutic targets specifically for pre‐existing drug‐resistant or highly tumorigenic clones. Colorectal cancer 2D patient‐derived cancer cells (PDCCs) and 3D air–liquid interface (ALI) organoids are established in this paper. This 2D and 3D model recapitulates histological, genomic and transcriptomic characteristics of parental tumors. Furthermore, the PDCCs show inter‐ and intratumoral heterogeneity of drug sensitivities and tumorigenicity. This 2D and 3D model can be applied to preclinical research more effectively and systematically.