Developing Organoids from Ovarian Cancer as Experimental and Preclinical Models.


Journal

Stem cell reports
ISSN: 2213-6711
Titre abrégé: Stem Cell Reports
Pays: United States
ID NLM: 101611300

Informations de publication

Date de publication:
14 04 2020
Historique:
received: 15 07 2019
revised: 03 03 2020
accepted: 03 03 2020
pubmed: 4 4 2020
medline: 26 3 2021
entrez: 4 4 2020
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 32243841
pii: S2213-6711(20)30094-1
doi: 10.1016/j.stemcr.2020.03.004
pmc: PMC7160357
pii:
doi:

Substances chimiques

Antineoplastic Agents 0
Neuregulin-1 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

717-729

Informations de copyright

Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

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Auteurs

Nina Maenhoudt (N)

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.

Charlotte Defraye (C)

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.

Matteo Boretto (M)

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.

Ziga Jan (Z)

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.

Ruben Heremans (R)

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; Gynecology and Obstetrics, University Hospitals Leuven (UZ Leuven), 3000 Leuven, Belgium.

Bram Boeckx (B)

Center for Cancer Biology, VIB, 3000 Leuven, Belgium; Laboratory for Translational Genetics, Department of Human Genetics, KU Leuven, 3000 Leuven, Belgium.

Florian Hermans (F)

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; Department of Morphology, Biomedical Research Institute, Faculty of Medicine and Life Sciences, Hasselt University, 3590 Diepenbeek, Belgium.

Ingrid Arijs (I)

Center for Cancer Biology, VIB, 3000 Leuven, Belgium; Laboratory for Translational Genetics, Department of Human Genetics, KU Leuven, 3000 Leuven, Belgium.

Benoit Cox (B)

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.

Els Van Nieuwenhuysen (E)

Cluster Woman and Child, Department of Development and Regeneration, KU Leuven, 3000 Leuven, Belgium; Gynecology and Obstetrics, University Hospitals Leuven (UZ Leuven), 3000 Leuven, Belgium.

Ignace Vergote (I)

Cluster Woman and Child, Department of Development and Regeneration, KU Leuven, 3000 Leuven, Belgium; Gynecology and Obstetrics, University Hospitals Leuven (UZ Leuven), 3000 Leuven, Belgium.

Anne-Sophie Van Rompuy (AS)

Translational Cell & Tissue Research, Department of Imaging & Pathology, KU Leuven, 3000 Leuven, Belgium.

Diether Lambrechts (D)

Center for Cancer Biology, VIB, 3000 Leuven, Belgium; Laboratory for Translational Genetics, Department of Human Genetics, KU Leuven, 3000 Leuven, Belgium.

Dirk Timmerman (D)

Cluster Woman and Child, Department of Development and Regeneration, KU Leuven, 3000 Leuven, Belgium; Gynecology and Obstetrics, University Hospitals Leuven (UZ Leuven), 3000 Leuven, Belgium.

Hugo Vankelecom (H)

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. Electronic address: hugo.vankelecom@kuleuven.be.

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