Patient-derived organoids model cervical tissue dynamics and viral oncogenesis in cervical cancer
Patient-derived organoids model cervical tissue dynamics and viral oncogenesis in cervical cancer
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DOI：
10.1016/j.stem.2021.03.012
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发表时间：
2021-08-05
期刊：
影响因子：
23.9
通讯作者：
Clevers, Hans
中科院分区：
文献类型：
--
作者：
Lohmussaar, Kadi;Oka, Rurika;Clevers, Hans
宫颈癌是一种常见的妇科恶性肿瘤，常由高危型人乳头瘤病毒引起。研究宫颈上皮及其衍生的癌症的人源性培养系统缺乏。在这里，我们描述了一个长期的培养方案，为外和宫颈上皮细胞，产生3D类器官，稳定地重演两个组织的起源。正如HSV-1所证明的那样，基于类器官的宫颈模型可以用于研究性传播感染。从巴氏刷材料开始，建立了一个来自受影响个体的类肿瘤的小型生物库，保留了致病性人乳头瘤病毒（HPV）基因组。其中一个独特地携带特征不佳的HPV 30亚型，这意味着在致癌作用中的潜在作用。类肿瘤对常见的化疗药物表现出不同的反应，并在小鼠中作为异种移植物生长。这项研究描述了一个实验平台，为宫颈（癌症）研究和未来的个性化医疗方法。
Cervical cancer is a common gynecological malignancy often caused by high-risk human papillomavirus. There is a paucity of human-derived culture systems to study the cervical epithelium and the cancers derived thereof. Here we describe a long-term culturing protocol for ecto- and endocervical epithelia that generates 3D organoids that stably recapitulate the two tissues of origin. As evidenced for HSV-1, organoid-based cervical models may serve to study sexually transmitted infections. Starting from Pap brush material, a small biobank of tumoroids derived from affected individuals was established that retained the causative human papillomavirus (HPV) genomes. One of these uniquely carried the poorly characterized HPV30 subtype, implying a potential role in carcinogenesis. The tumoroids displayed differential responses to common chemotherapeutic agents and grew as xenografts in mice. This study describes an experimental platform for cervical (cancer) research and for future personalized medicine approaches.