Patient-Derived Organoid Models of Human Neuroendocrine Carcinoma

Krijn K. Dijkstra, José G. van den Berg, Fleur Weeber, Joris van de Haar, Arno Velds, Sovann Kaing, Dennis D.G.C. Peters, Ferry A.L.M. Eskens, Derk Jan A. de Groot, Margot E.T. Tesselaar, Emile E. Voest*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

19 Citations (Scopus)
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Abstract

Gastroenteropancreatic neuroendocrine carcinoma (GEP-NEC) is a poorly understood disease with limited treatment options. A better understanding of this disease would greatly benefit from the availability of representative preclinical models. Here, we present the potential of tumor organoids, three-dimensional cultures of tumor cells, to model GEP-NEC. We established three GEP-NEC organoid lines, originating from the stomach and colon, and characterized them using DNA sequencing and immunohistochemistry. Organoids largely resembled the original tumor in expression of synaptophysin, chromogranin and Ki-67. Models derived from tumors containing both neuroendocrine and non-neuroendocrine components were at risk of overgrowth by non-neuroendocrine tumor cells. Organoids were derived from patients treated with cisplatin and everolimus and for the three patients studied, organoid chemosensitivity paralleled clinical response. We demonstrate the feasibility of establishing NEC organoid lines and their potential applications. Organoid culture has the potential to greatly extend the repertoire of preclinical models for GEP-NEC, supporting drug development for this difficult-to-treat tumor type.

Original languageEnglish
Article number627819
JournalFrontiers in Endocrinology
Volume12
DOIs
Publication statusPublished - 11 Mar 2021

Bibliographical note

Funding Information:
We thank Judith Westra, Sandra Visser, Louisa Hoes, Luuk Schipper, and Daphne van der Velden for help with acquisition of human samples. We acknowledge Ingrid Hofland and Annegien Broeks and other members of the NKI-AVL Core Facility Molecular Pathology & Biobank (CFMPB) for supplying NKI-AVL Biobank material and lab support. We thank Ron Kerkhoven, Marja Nieuwland, Roel Kluin, Charlaine Steenis, and Wim Brugman for DNA sequencing and analysis. We thank Loes van Velthuysen for providing immunohistochemistry slides.

Publisher Copyright:
© Copyright © 2021 Dijkstra, van den Berg, Weeber, van de Haar, Velds, Kaing, Peters, Eskens, de Groot, Tesselaar and Voest.

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