Establishment and characterization of a cell line and patient-derived xenograft (PDX) from peritoneal metastasis of low-grade serous ovarian carcinoma

Abstract Peritoneal spread indicates poor prognosis in patients with serous ovarian carcinoma (SOC) and is generally treated by surgical cytoreduction and chemotherapy. Novel treatment options are urgently needed to improve patient outcome. Clinically relevant cell lines and patient-derived xenograf...

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Autores principales:	Elien De Thaye, Koen Van de Vijver, Joni Van der Meulen, Joachim Taminau, Glenn Wagemans, Hannelore Denys, Jo Van Dorpe, Geert Berx, Wim Ceelen, Jan Van Bocxlaer, Olivier De Wever
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/06dcae893d8f4e05a6164052d60339cc
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spelling	oai:doaj.org-article:06dcae893d8f4e05a6164052d60339cc2021-12-02T18:27:50ZEstablishment and characterization of a cell line and patient-derived xenograft (PDX) from peritoneal metastasis of low-grade serous ovarian carcinoma10.1038/s41598-020-63738-62045-2322https://doaj.org/article/06dcae893d8f4e05a6164052d60339cc2020-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-63738-6https://doaj.org/toc/2045-2322Abstract Peritoneal spread indicates poor prognosis in patients with serous ovarian carcinoma (SOC) and is generally treated by surgical cytoreduction and chemotherapy. Novel treatment options are urgently needed to improve patient outcome. Clinically relevant cell lines and patient-derived xenograft (PDX) models are of critical importance to therapeutic regimen evaluation. Here, a PDX model was established, by orthotopic engraftment after subperitoneal tumor slurry injection of low-grade SOC, resulting in an early-stage transplantable peritoneal metastasis (PM)-PDX model. Histology confirmed the micropapillary and cribriform growth pattern with intraluminal tumor budding and positivity for PAX8 and WT1. PM-PDX dissociated cells show an epithelial morphotype with a 42 h doubling time and 40% colony forming efficiency, they are low sensitive to platinum derivatives and highly sensitive to paclitaxel (IC50: 6.3 ± 2.2 nM, mean ± SEM). The patient primary tumor, PM, PM-PDX and derived cell line all show a KRAS c.35 G > T (p.(Gly12Val)) mutation and show sensitivity to the MEK inhibitor trametinib in vitro (IC50: 7.2 ± 0.5 nM, mean ± SEM) and in the PM mouse model. These preclinical models closely reflecting patient tumors are useful to further elucidate LGSOC disease progression, therapy response and resistance mechanisms.Elien De ThayeKoen Van de VijverJoni Van der MeulenJoachim TaminauGlenn WagemansHannelore DenysJo Van DorpeGeert BerxWim CeelenJan Van BocxlaerOlivier De WeverNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-10 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Elien De Thaye Koen Van de Vijver Joni Van der Meulen Joachim Taminau Glenn Wagemans Hannelore Denys Jo Van Dorpe Geert Berx Wim Ceelen Jan Van Bocxlaer Olivier De Wever Establishment and characterization of a cell line and patient-derived xenograft (PDX) from peritoneal metastasis of low-grade serous ovarian carcinoma
description	Abstract Peritoneal spread indicates poor prognosis in patients with serous ovarian carcinoma (SOC) and is generally treated by surgical cytoreduction and chemotherapy. Novel treatment options are urgently needed to improve patient outcome. Clinically relevant cell lines and patient-derived xenograft (PDX) models are of critical importance to therapeutic regimen evaluation. Here, a PDX model was established, by orthotopic engraftment after subperitoneal tumor slurry injection of low-grade SOC, resulting in an early-stage transplantable peritoneal metastasis (PM)-PDX model. Histology confirmed the micropapillary and cribriform growth pattern with intraluminal tumor budding and positivity for PAX8 and WT1. PM-PDX dissociated cells show an epithelial morphotype with a 42 h doubling time and 40% colony forming efficiency, they are low sensitive to platinum derivatives and highly sensitive to paclitaxel (IC50: 6.3 ± 2.2 nM, mean ± SEM). The patient primary tumor, PM, PM-PDX and derived cell line all show a KRAS c.35 G > T (p.(Gly12Val)) mutation and show sensitivity to the MEK inhibitor trametinib in vitro (IC50: 7.2 ± 0.5 nM, mean ± SEM) and in the PM mouse model. These preclinical models closely reflecting patient tumors are useful to further elucidate LGSOC disease progression, therapy response and resistance mechanisms.
format	article
author	Elien De Thaye Koen Van de Vijver Joni Van der Meulen Joachim Taminau Glenn Wagemans Hannelore Denys Jo Van Dorpe Geert Berx Wim Ceelen Jan Van Bocxlaer Olivier De Wever
author_facet	Elien De Thaye Koen Van de Vijver Joni Van der Meulen Joachim Taminau Glenn Wagemans Hannelore Denys Jo Van Dorpe Geert Berx Wim Ceelen Jan Van Bocxlaer Olivier De Wever
author_sort	Elien De Thaye
title	Establishment and characterization of a cell line and patient-derived xenograft (PDX) from peritoneal metastasis of low-grade serous ovarian carcinoma
title_short	Establishment and characterization of a cell line and patient-derived xenograft (PDX) from peritoneal metastasis of low-grade serous ovarian carcinoma
title_full	Establishment and characterization of a cell line and patient-derived xenograft (PDX) from peritoneal metastasis of low-grade serous ovarian carcinoma
title_fullStr	Establishment and characterization of a cell line and patient-derived xenograft (PDX) from peritoneal metastasis of low-grade serous ovarian carcinoma
title_full_unstemmed	Establishment and characterization of a cell line and patient-derived xenograft (PDX) from peritoneal metastasis of low-grade serous ovarian carcinoma
title_sort	establishment and characterization of a cell line and patient-derived xenograft (pdx) from peritoneal metastasis of low-grade serous ovarian carcinoma
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/06dcae893d8f4e05a6164052d60339cc
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Establishment and characterization of a cell line and patient-derived xenograft (PDX) from peritoneal metastasis of low-grade serous ovarian carcinoma

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