A three-dimensional organoid model recapitulates tumorigenic aspects and drug responses of advanced human retinoblastoma

Abstract Persistent or recurrent retinoblastoma (RB) is associated with the presence of vitreous or/and subretinal seeds in advanced RB and represents a major cause of therapeutic failure. This necessitates the development of novel therapies and thus requires a model of advanced RB for testing candi...

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Autores principales:	Duangporn Saengwimol, Duangnate Rojanaporn, Vijender Chaitankar, Pamorn Chittavanich, Rangsima Aroonroch, Tatpong Boontawon, Weerin Thammachote, Natini Jinawath, Suradej Hongeng, Rossukon Kaewkhaw
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Organoid Models Retinal Tumors Subretinal Seeds Combined Drug Regimens Topotecan Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7055f181010d4848b2eaf2b999543e4e
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spelling	oai:doaj.org-article:7055f181010d4848b2eaf2b999543e4e2021-12-02T15:08:15ZA three-dimensional organoid model recapitulates tumorigenic aspects and drug responses of advanced human retinoblastoma10.1038/s41598-018-34037-y2045-2322https://doaj.org/article/7055f181010d4848b2eaf2b999543e4e2018-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-34037-yhttps://doaj.org/toc/2045-2322Abstract Persistent or recurrent retinoblastoma (RB) is associated with the presence of vitreous or/and subretinal seeds in advanced RB and represents a major cause of therapeutic failure. This necessitates the development of novel therapies and thus requires a model of advanced RB for testing candidate therapeutics. To this aim, we established and characterized a three-dimensional, self-organizing organoid model derived from chemotherapy-naïve tumors. The responses of organoids to drugs were determined and compared to relate organoid model to advanced RB, in terms of drug sensitivities. We found that organoids had histological features resembling retinal tumors and seeds and retained DNA copy-number alterations as well as gene and protein expression of the parental tissue. Cone signal circuitry (M/L+ cells) and glial tumor microenvironment (GFAP+ cells) were primarily present in organoids. Topotecan alone or the combined drug regimen of topotecan and melphalan effectively targeted proliferative tumor cones (RXRγ+ Ki67+) in organoids after 24-h drug exposure, blocking mitotic entry. In contrast, methotrexate showed the least efficacy against tumor cells. The drug responses of organoids were consistent with those of tumor cells in advanced disease. Patient-derived organoids enable the creation of a faithful model to use in examining novel therapeutics for RB.Duangporn SaengwimolDuangnate RojanapornVijender ChaitankarPamorn ChittavanichRangsima AroonrochTatpong BoontawonWeerin ThammachoteNatini JinawathSuradej HongengRossukon KaewkhawNature PortfolioarticleOrganoid ModelsRetinal TumorsSubretinal SeedsCombined Drug RegimensTopotecanMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-13 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Organoid Models Retinal Tumors Subretinal Seeds Combined Drug Regimens Topotecan Medicine R Science Q
spellingShingle	Organoid Models Retinal Tumors Subretinal Seeds Combined Drug Regimens Topotecan Medicine R Science Q Duangporn Saengwimol Duangnate Rojanaporn Vijender Chaitankar Pamorn Chittavanich Rangsima Aroonroch Tatpong Boontawon Weerin Thammachote Natini Jinawath Suradej Hongeng Rossukon Kaewkhaw A three-dimensional organoid model recapitulates tumorigenic aspects and drug responses of advanced human retinoblastoma
description	Abstract Persistent or recurrent retinoblastoma (RB) is associated with the presence of vitreous or/and subretinal seeds in advanced RB and represents a major cause of therapeutic failure. This necessitates the development of novel therapies and thus requires a model of advanced RB for testing candidate therapeutics. To this aim, we established and characterized a three-dimensional, self-organizing organoid model derived from chemotherapy-naïve tumors. The responses of organoids to drugs were determined and compared to relate organoid model to advanced RB, in terms of drug sensitivities. We found that organoids had histological features resembling retinal tumors and seeds and retained DNA copy-number alterations as well as gene and protein expression of the parental tissue. Cone signal circuitry (M/L+ cells) and glial tumor microenvironment (GFAP+ cells) were primarily present in organoids. Topotecan alone or the combined drug regimen of topotecan and melphalan effectively targeted proliferative tumor cones (RXRγ+ Ki67+) in organoids after 24-h drug exposure, blocking mitotic entry. In contrast, methotrexate showed the least efficacy against tumor cells. The drug responses of organoids were consistent with those of tumor cells in advanced disease. Patient-derived organoids enable the creation of a faithful model to use in examining novel therapeutics for RB.
format	article
author	Duangporn Saengwimol Duangnate Rojanaporn Vijender Chaitankar Pamorn Chittavanich Rangsima Aroonroch Tatpong Boontawon Weerin Thammachote Natini Jinawath Suradej Hongeng Rossukon Kaewkhaw
author_facet	Duangporn Saengwimol Duangnate Rojanaporn Vijender Chaitankar Pamorn Chittavanich Rangsima Aroonroch Tatpong Boontawon Weerin Thammachote Natini Jinawath Suradej Hongeng Rossukon Kaewkhaw
author_sort	Duangporn Saengwimol
title	A three-dimensional organoid model recapitulates tumorigenic aspects and drug responses of advanced human retinoblastoma
title_short	A three-dimensional organoid model recapitulates tumorigenic aspects and drug responses of advanced human retinoblastoma
title_full	A three-dimensional organoid model recapitulates tumorigenic aspects and drug responses of advanced human retinoblastoma
title_fullStr	A three-dimensional organoid model recapitulates tumorigenic aspects and drug responses of advanced human retinoblastoma
title_full_unstemmed	A three-dimensional organoid model recapitulates tumorigenic aspects and drug responses of advanced human retinoblastoma
title_sort	three-dimensional organoid model recapitulates tumorigenic aspects and drug responses of advanced human retinoblastoma
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/7055f181010d4848b2eaf2b999543e4e
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A three-dimensional organoid model recapitulates tumorigenic aspects and drug responses of advanced human retinoblastoma

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