Gynecology Oncology Research Group, School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, New South Wales, 2308, Australia.
School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, 2308, Australia.
Proteomics. 2019 Nov;19(21-22):e1800448. doi: 10.1002/pmic.201800448. Epub 2019 May 7.
Epithelial and stromal communications are essential for normal uterine functions and their dysregulation contributes to the pathogenesis of many diseases including infertility, endometriosis, and cancer. Although many studies have highlighted the advantages of culturing cells in 3D compared to the conventional 2D culture system, one of the major limitations of these systems is the lack of incorporation of cells from non-epithelial lineages. In an effort to develop a culture system incorporating both stromal and epithelial cells, 3D endometrial cancer spheroids are developed by co-culturing endometrial stromal cells with cancerous epithelial cells. The spheroids developed by this method are phenotypically comparable to in vivo endometrial cancer tissue. Proteomic analysis of the co-culture spheroids comparable to human endometrial tissue revealed 591 common proteins and canonical pathways that are closely related to endometrium biology. To determine the feasibility of using this model for drug screening, the efficacy of tamoxifen and everolimus is tested. In summary, a unique 3D model system of human endometrial cancer is developed that will serve as the foundation for the further development of 3D culture systems incorporating different cell types of the human uterus for deciphering the contributions of non-epithelial cells present in cancer microenvironment.
上皮和基质之间的交流对于子宫的正常功能至关重要，其失调会导致许多疾病的发病机制，包括不孕、子宫内膜异位症和癌症。尽管许多研究强调了将细胞在 3D 中培养相对于传统的 2D 培养系统的优势，但这些系统的主要局限性之一是缺乏非上皮谱系细胞的掺入。为了开发一种同时包含基质和上皮细胞的培养系统，通过共培养子宫内膜基质细胞和癌变上皮细胞来开发 3D 子宫内膜癌细胞球体。通过这种方法开发的球体在表型上与体内子宫内膜癌组织相当。与人类子宫内膜组织相当的共培养球体的蛋白质组学分析揭示了 591 种常见蛋白质和与子宫内膜生物学密切相关的经典途径。为了确定使用该模型进行药物筛选的可行性，测试了他莫昔芬和依维莫司的疗效。总之，开发了一种独特的人子宫内膜癌 3D 模型系统，它将为进一步开发包含人子宫不同细胞类型的 3D 培养系统奠定基础，以破译癌症微环境中存在的非上皮细胞的贡献。
