Primary liver cancer, consisting predominantly of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), remains one of the most lethal malignancies worldwide. This high malignancy is related to the complex and dynamic interactions between tumour cells, stromal cells and the extracellular environment. Novel in vitro models that can recapitulate the tumour are essential in increasing our understanding of liver cancer. Herein, primary liver cancer-derived organoids have opened up new avenues due to their patient-specificity, self-organizing ability and potential recapitulation of many of the tumour properties. Organoids are solely of epithelial origin, but incorporation into co-culture models can enable the investigation of the cellular component of the tumour microenvironment. However, the extracellular component also plays a vital role in cancer progression and representation is lacking within current in vitro models. In this review, organoid technology is discussed in the context of liver cancer models through comparisons to other cell culture systems. In addition, the role of the tumour extracellular environment in primary liver cancer will be highlighted with an emphasis on its importance in in vitro modelling. Converging novel organoid-based models with models incorporating the native tumour microenvironment could lead to experimental models that can better recapitulate liver tumours in vivo.

译文

原发性肝癌主要由肝细胞癌(HCC)和胆管癌(CCA)组成,仍然是全球最致命的恶性肿瘤之一。这种高恶性与肿瘤细胞,基质细胞和细胞外环境之间复杂而动态的相互作用有关。可以概括肿瘤的新型体外模型对于增进我们对肝癌的了解至关重要。在本文中,原发性肝癌衍生的类器官由于其患者特异性,自组织能力和许多肿瘤特性的潜在概括而开辟了新途径。类器官仅是上皮来源的,但是掺入共培养模型可以研究肿瘤微环境的细胞成分。但是,细胞外成分在癌症进展中也起着至关重要的作用,目前的体外模型中缺乏这种表现形式。在这篇综述中,通过与其他细胞培养系统进行比较,在肝癌模型的背景下讨论类器官技术。另外,将强调肿瘤细胞外环境在原发性肝癌中的作用,并强调其在体外建模中的重要性。将基于类器官的新型模型与结合了天然肿瘤微环境的模型进行融合,可以产生能够更好地在体内概括肝肿瘤的实验模型。

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