The three-dimensional (3D) cell culture technique has been applied comprehensively as a variable platform for medical research, biochemical signal pathway analysis, and evaluation of anti-tumor treatment response due to an excellent recapitulation of a tumor microenvironment (TME) in the in vitro cultured cancer cells. Pancreatic cancer (PaC) is one of the toughest malignancies with a complex TME and refractory treatment response. To comprehensively study the TME of PaC, there is an eager need to develop a 3D culture model to decompose the cellular components and their cross interactions. Herein, we establish a 3D PaC culture system with cancer stem cell (CSC) and scalability properties. To validate our model, we tested the individual PaC cell and the combined effects with cancer-associated fibroblasts (CAFs) on cancer tumorigenicity, the cellular interaction through the CXCR3/CXCL10 axis, and cellular responses reflection of anti-cancer treatments. With the help of our 3D technology, a simulated malignant spheroid with important stromal populations and TME physiochemical properties may be successfully recreated. It can be used in a wide range of preclinical research and helpful in advancing basic and translational cancer biology.

中文翻译：

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三维培养体系中胰腺癌细胞致瘤性、球体微环境和耐药性的增强

三维（3D）细胞培养技术由于对肿瘤微环境（TME）的出色再现，已作为医学研究、生化信号通路分析和抗肿瘤治疗反应评估的可变平台得到全面应用。体外培养的癌细胞。胰腺癌 (PaC) 是最棘手的恶性肿瘤之一，具有复杂的 TME 和难治性的治疗反应。为了全面研究 PaC 的 TME，迫切需要开发 3D 培养模型来分解细胞成分及其交叉相互作用。在此，我们建立了具有癌症干细胞 (CSC) 和可扩展特性的 3D PaC 培养系统。为了验证我们的模型，我们测试了单个 PaC 细胞以及与癌症相关成纤维细胞 (CAF) 对癌症致瘤性、通过 CXCR3/CXCL10 轴的细胞相互作用以及抗癌治疗的细胞反应反映的综合影响。借助我们的 3D 技术，可以成功地重建具有重要基质群体和 TME 理化特性的模拟恶性球体。它可用于广泛的临床前研究，有助于推进基础和转化癌症生物学。