Laboratory of Tissue Plasticity in Health and Disease, Cluster of Stem Cell and Developmental Biology, Department of Development and Regeneration, KU Leuven (University of Leuven), 3000 Leuven, Belgium.
Laboratory of Tissue Plasticity in Health and Disease, Cluster of Stem Cell and Developmental Biology, Department of Development and Regeneration, KU Leuven (University of Leuven), 3000 Leuven, Belgium; Cluster Woman and Child, Department of Development and Regeneration, KU Leuven, 3000 Leuven, Belgium; Cancer Centre Carinthia, 9020 Klagenfurt, Austria.
Stem Cell Reports. 2020 Apr 14;14(4):717-729. doi: 10.1016/j.stemcr.2020.03.004. Epub 2020 Apr 2.
Ovarian cancer (OC) represents the most dismal gynecological cancer. Pathobiology is poorly understood, mainly due to lack of appropriate study models. Organoids, defined as self-developing three-dimensional in vitro reconstructions of tissues, provide powerful tools to model human diseases. Here, we established organoid cultures from patient-derived OC, in particular from the most prevalent high-grade serous OC (HGSOC). Testing multiple culture medium components identified neuregulin-1 (NRG1) as key factor in maximizing OC organoid development and growth, although overall derivation efficiency remained moderate (36% for HGSOC patients, 44% for all patients together). Established organoid lines showed patient tumor-dependent morphology and disease characteristics, and recapitulated the parent tumor's marker expression and mutational landscape. Moreover, the organoids displayed tumor-specific sensitivity to clinical HGSOC chemotherapeutic drugs. Patient-derived OC organoids provide powerful tools for the study of the cancer's pathobiology (such as importance of the NRG1/ERBB pathway) as well as advanced preclinical tools for (personalized) drug screening and discovery.
卵巢癌（OC）是最致命的妇科癌症。其病理生物学机制尚未完全阐明，主要是因为缺乏合适的研究模型。类器官是指在体外自我发育的三维组织重建，为模拟人类疾病提供了强大的工具。在这里，我们从患者来源的 OC 中建立了类器官培养物，特别是最常见的高级别浆液性 OC（HGSOC）。通过测试多种培养基成分，我们确定神经调节蛋白 1（NRG1）是最大限度地促进 OC 类器官发育和生长的关键因素，尽管总体的衍生效率仍然适中（HGSOC 患者为 36%，所有患者为 44%）。建立的类器官系表现出患者肿瘤依赖性的形态和疾病特征，并再现了亲本肿瘤的标志物表达和突变景观。此外，这些类器官对临床 HGSOC 化疗药物表现出肿瘤特异性敏感性。患者来源的 OC 类器官为研究癌症的病理生物学（如 NRG1/ERBB 通路的重要性）提供了强大的工具，并且为（个性化）药物筛选和发现提供了先进的临床前工具。
