P6: Studying clinical implications of altered epigenetics using urothelial carcinoma organoid models

P6：使用尿路上皮癌类器官模型研究表观遗传学改变的临床意义

• 批准号: 526184989
• 负责人: Professor Dr. Christian Gratzke
• 金额: --
• 依托单位: Klinik für Urologie
• 依托单位国家: 德国
• 项目类别: Research Units
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/526184989?language=en
• 关键词: P6; Studying; clinical; implications; altered

Recently, three-dimensional organoid culture systems of primary bladder cancer cells have been developed to overcome the limitations of cell lines and importantly to permit the direct study of patient-derived tumor samples in cell culture. Organoids are defined as 3D constructs which recapitulate many physiological characteristics of their corresponding in vivo organs, which highlights their potential for identifying therapeutic targets and verifying drug response. In this project we will utilize urothelial carcinoma organoids to study the clinical and biological implications of altered epigenetics in urothelial carcinomas, to study interactions between cancer associated fibroblasts and tumor cells and to test therapeutic responses to new epigenetically targeted therapies that will be developed by other groups in the UcarE Research Unit. To our knowledge, no organoid from metastatic bladder cancer tissue has yet been established. Using our established protocols, we aim to establish human bladder cancer organoids from both primary bladder cancer as well as from metastatic tissue. Our goal is to establish a living biobank of human bladder cancer organoid lines reflecting different stages of disease progression and encompassing different combinations of cancer driver genes, including epigenetic tumor suppressor genes. By phenotypically (histology and immunofluorescence staining), molecularly (RNA-seq) and genetically (Exome-seq) characterizing the organoids, we will establish a highly value-added urothelial carcinoma biobank that will be useful for all UcarE projects as well as more generally for the research community studying bladder cancer.

最近，开发了原发性膀胱癌细胞的三维类器官培养系统，以克服细胞系的局限性，重要的是允许在细胞培养中直接研究源自患者的肿瘤样本。类器官被定义为 3D 构建体，它概括了相应体内器官的许多生理特征，这凸显了它们在识别治疗靶点和验证药物反应方面的潜力。在这个项目中，我们将利用尿路上皮癌类器官来研究尿路上皮癌表观遗传学改变的临床和生物学影响，研究癌症相关成纤维细胞和肿瘤细胞之间的相互作用，并测试对其他小组将开发的新表观遗传学靶向疗法的治疗反应在 UcarE 研究单位。据我们所知，尚未建立来自转移性膀胱癌组织的类器官。使用我们既定的方案，我们的目标是从原发性膀胱癌和转移组织中建立人类膀胱癌类器官。我们的目标是建立人类膀胱癌类器官系的活体生物库，反映疾病进展的不同阶段，并包含癌症驱动基因的不同组合，包括表观遗传肿瘤抑制基因。通过对类器官进行表型（组织学和免疫荧光染色）、分子（RNA-seq）和遗传学（Exome-seq）表征，我们将建立一个高附加值的尿路上皮癌生物库，该生物库将适用于所有 UcarE 项目以及更广泛的领域供研究膀胱癌的研究团体使用。