An organoid platform for ovarian cancer captures intra- and interpatient heterogeneity.,Nature Medicine

当前位置： X-MOL 学术 › Nat. Med. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

An organoid platform for ovarian cancer captures intra- and interpatient heterogeneity.
Nature Medicine ( IF 58.7 ) Pub Date : 2019-04-22 , DOI: 10.1038/s41591-019-0422-6
Oded Kopper _{1,

2} , Chris J de Witte ₃ , Kadi Lõhmussaar _{1,

2} , Jose Espejo Valle-Inclan ₃ , Nizar Hami _{2,

4} , Lennart Kester _{1,

2} , Anjali Vanita Balgobind _{1,

2} , Jeroen Korving _{1,

2} , Natalie Proost ₅ , Harry Begthel _{1,

2} , Lise M van Wijk ₆ , Sonia Aristín Revilla _{1,

2} , Rebecca Theeuwsen ₅ , Marieke van de Ven ₅ , Markus J van Roosmalen ₃ , Bas Ponsioen _{2,

4} , Victor W H Ho ₇ , Benjamin G Neel _{7,

8} , Tjalling Bosse ₉ , Katja N Gaarenstroom ₁₀ , Harry Vrieling ₆ , Maaike P G Vreeswijk ₆ , Paul J van Diest ₁₁ , Petronella O Witteveen ₁₂ , Trudy Jonges ₁₁ , Johannes L Bos _{2,

4} , Alexander van Oudenaarden _{1,

2} , Ronald P Zweemer ₁₃ , Hugo J G Snippert _{2,

4} , Wigard P Kloosterman ₃ , Hans Clevers _{1,

2,

14}

Affiliation

Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and UMC Utrecht, Utrecht, the Netherlands.
Oncode Institute, Utrecht, the Netherlands.
Center for Molecular Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
Molecular Cancer Research, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
Preclinical Intervention Unit of the Mouse Clinic for Cancer and Ageing (MCCA) at the NKI, Amsterdam, the Netherlands.
Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands.
Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada.
Perlmutter Cancer Center, NYU Langone Health, New York, NY, USA.
Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands.
Department of Gynecology, Leiden University Medical Center, Leiden, the Netherlands.
Department of Pathology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
Department of Medical Oncology, Cancer Center, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
Department of Gynaecological Oncology, Cancer Center, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
The Netherlands Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.

Ovarian cancer (OC) is a heterogeneous disease usually diagnosed at a late stage. Experimental in vitro models that faithfully capture the hallmarks and tumor heterogeneity of OC are limited and hard to establish. We present a protocol that enables efficient derivation and long-term expansion of OC organoids. Utilizing this protocol, we have established 56 organoid lines from 32 patients, representing all main subtypes of OC. OC organoids recapitulate histological and genomic features of the pertinent lesion from which they were derived, illustrating intra- and interpatient heterogeneity, and can be genetically modified. We show that OC organoids can be used for drug-screening assays and capture different tumor subtype responses to the gold standard platinum-based chemotherapy, including acquisition of chemoresistance in recurrent disease. Finally, OC organoids can be xenografted, enabling in vivo drug-sensitivity assays. Taken together, this demonstrates their potential application for research and personalized medicine.

中文翻译：

卵巢癌的类器官平台可捕获患者内和患者间的异质性。

卵巢癌（OC）是一种异质性疾病，通常在晚期被诊断出。忠实捕获OC标志和肿瘤异质性的体外实验模型有限且难以建立。我们提出了一个协议，该协议可以实现OC类器官的有效派生和长期扩展。利用该方案，我们从32位患者中建立了56个类器官，代表了OC的所有主要亚型。OC类器官概述了其起源的相关病变的组织学和基因组学特征，说明了患者内和患者间的异质性，并且可以进行基因修饰。我们显示OC类器官可用于药物筛选测定，并捕获对金标准基于铂的化学疗法的不同肿瘤亚型反应，包括在复发性疾病中获得化学耐药性。最后，OC类器官可以异种移植，从而可以进行体内药物敏感性测定。综上所述，这表明了它们在研究和个性化医学方面的潜在应用。

更新日期：2019-05-16

点击分享查看原文

点击收藏

阅读更多本刊新发论文本刊介绍/投稿指南