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

doi:10.3389/fendo.2021.627819

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

Medical Oncology

Research output: Contribution to journal › Article › Academic › peer-review

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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 language	English
Article number	627819
Journal	Frontiers in Endocrinology
Volume	12
DOIs	https://doi.org/10.3389/fendo.2021.627819
Publication status	Published - 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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Cite this

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title = "Patient-Derived Organoid Models of Human Neuroendocrine Carcinoma",

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.",

author = "Dijkstra, {Krijn K.} and {van den Berg}, {Jos{\'e} G.} and Fleur Weeber and {van de Haar}, Joris and Arno Velds and Sovann Kaing and Peters, {Dennis D.G.C.} and Eskens, {Ferry A.L.M.} and {de Groot}, {Derk Jan A.} and Tesselaar, {Margot E.T.} and Voest, {Emile E.}",

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: {\textcopyright} Copyright {\textcopyright} 2021 Dijkstra, van den Berg, Weeber, van de Haar, Velds, Kaing, Peters, Eskens, de Groot, Tesselaar and Voest.",

year = "2021",

month = mar,

day = "11",

doi = "10.3389/fendo.2021.627819",

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AU - Dijkstra, Krijn K.

AU - van den Berg, José G.

AU - Weeber, Fleur

AU - van de Haar, Joris

AU - Velds, Arno

AU - Kaing, Sovann

AU - Peters, Dennis D.G.C.

AU - Eskens, Ferry A.L.M.

AU - de Groot, Derk Jan A.

AU - Tesselaar, Margot E.T.

AU - Voest, Emile E.

N1 - 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.

PY - 2021/3/11

Y1 - 2021/3/11

N2 - 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.

AB - 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.

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U2 - 10.3389/fendo.2021.627819

DO - 10.3389/fendo.2021.627819

M3 - Article

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SN - 1664-2392

VL - 12

JO - Frontiers in Endocrinology

JF - Frontiers in Endocrinology

M1 - 627819

ER -

Patient-Derived Organoid Models of Human Neuroendocrine Carcinoma

Abstract

Bibliographical note

UN SDGs

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