The tumour microenvironment is critical to both the initiation and maintenance of tumorigenesis. Reconstitution of the microenvironment is a major challenge for in vitro cancer models. Indeed, conventional 2D culture systems cannot replicate the complexity, diversity and dynamic nature of the tumour microenvironment. In this study, we have developed a 3D endotheliazed vesical equivalent by using tissue engineering from primary human cells in which non-invasive or invasive bladder cancer (BCa) cell lines, cultured as compact spheroids, were incorporated. Invasive BCa cells cross the basement membrane and invade the stromal compartment whereas non-invasive BCa cells are confined to the urothelium. Our 3D BCa model could be used as a reliable model for assessing drug responses, potentially reducing or partially replacing animal experiments, and thus should have applications in the identification of novel targets as well as toxicological evaluation of anti-cancer therapies.

中文翻译：

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组织工程化的人类3D膀胱癌3D模型用于入侵研究和药物发现

肿瘤微环境对于引发和维持肿瘤发生均至关重要。微环境的重构是体外的主要挑战癌症模型。实际上，常规的2D培养系统无法复制肿瘤微环境的复杂性，多样性和动态性质。在这项研究中，我们已经通过使用原代人细胞的组织工程技术开发了3D内皮囊泡等效物，其中将非侵入性或浸润性膀胱癌（BCa）细胞系培养成紧密的球状体。侵袭性BCa细胞穿过基底膜并侵入基质区隔，而非侵袭性BCa细胞则局限于尿路上皮。我们的3D BCa模型可用作评估药物反应，潜在减少或部分替代动物实验的可靠模型，因此应在鉴定新靶标以及抗癌疗法的毒理学评估中得到应用。