Modeling Prostate Cancer Treatment Responses in the Organoid Era: 3D Environment Impacts Drug Testing

Organoid-based studies have revolutionized in vitro preclinical research and hold great promise for the cancer research field, including prostate cancer (PCa). However, experimental variability in organoid drug testing complicates reproducibility. For example, we observed PCa organoids to be less af...

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Autores principales:	Annelies Van Hemelryk, Lisanne Mout, Sigrun Erkens-Schulze, Pim J. French, Wytske M. van Weerden, Martin E. van Royen
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	prostate cancer CRPC organoid 3D cell culture preclinical models live-cell imaging Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/721bef334d5b4664922d111ed7466a0c
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spelling	oai:doaj.org-article:721bef334d5b4664922d111ed7466a0c2021-11-25T16:52:03ZModeling Prostate Cancer Treatment Responses in the Organoid Era: 3D Environment Impacts Drug Testing10.3390/biom111115722218-273Xhttps://doaj.org/article/721bef334d5b4664922d111ed7466a0c2021-10-01T00:00:00Zhttps://www.mdpi.com/2218-273X/11/11/1572https://doaj.org/toc/2218-273XOrganoid-based studies have revolutionized in vitro preclinical research and hold great promise for the cancer research field, including prostate cancer (PCa). However, experimental variability in organoid drug testing complicates reproducibility. For example, we observed PCa organoids to be less affected by cabazitaxel, abiraterone and enzalutamide as compared to corresponding single cells prior to organoid assembly. We hypothesized that three-dimensional (3D) organoid organization and the use of various 3D scaffolds impact treatment efficacy. Live-cell imaging of androgen-induced androgen receptor (AR) nuclear translocation and taxane-induced tubulin stabilization was used to investigate the impact of 3D scaffolds, spatial organoid distribution and organoid size on treatment effect. Scaffolds delayed AR translocation and tubulin stabilization, with Matrigel causing a more pronounced delay than synthetic hydrogel as well as incomplete tubulin stabilization. Drug effect was further attenuated the more centrally organoids were located in the scaffold dome. Moreover, cells in the organoid core revealed a delayed treatment effect compared to cells in the organoid periphery, underscoring the impact of organoid size. These findings indicate that analysis of organoid drug responses needs careful interpretation and requires dedicated read-outs with consideration of underlying technical aspects.Annelies Van HemelrykLisanne MoutSigrun Erkens-SchulzePim J. FrenchWytske M. van WeerdenMartin E. van RoyenMDPI AGarticleprostate cancerCRPCorganoid3D cell culturepreclinical modelslive-cell imagingMicrobiologyQR1-502ENBiomolecules, Vol 11, Iss 1572, p 1572 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	prostate cancer CRPC organoid 3D cell culture preclinical models live-cell imaging Microbiology QR1-502
spellingShingle	prostate cancer CRPC organoid 3D cell culture preclinical models live-cell imaging Microbiology QR1-502 Annelies Van Hemelryk Lisanne Mout Sigrun Erkens-Schulze Pim J. French Wytske M. van Weerden Martin E. van Royen Modeling Prostate Cancer Treatment Responses in the Organoid Era: 3D Environment Impacts Drug Testing
description	Organoid-based studies have revolutionized in vitro preclinical research and hold great promise for the cancer research field, including prostate cancer (PCa). However, experimental variability in organoid drug testing complicates reproducibility. For example, we observed PCa organoids to be less affected by cabazitaxel, abiraterone and enzalutamide as compared to corresponding single cells prior to organoid assembly. We hypothesized that three-dimensional (3D) organoid organization and the use of various 3D scaffolds impact treatment efficacy. Live-cell imaging of androgen-induced androgen receptor (AR) nuclear translocation and taxane-induced tubulin stabilization was used to investigate the impact of 3D scaffolds, spatial organoid distribution and organoid size on treatment effect. Scaffolds delayed AR translocation and tubulin stabilization, with Matrigel causing a more pronounced delay than synthetic hydrogel as well as incomplete tubulin stabilization. Drug effect was further attenuated the more centrally organoids were located in the scaffold dome. Moreover, cells in the organoid core revealed a delayed treatment effect compared to cells in the organoid periphery, underscoring the impact of organoid size. These findings indicate that analysis of organoid drug responses needs careful interpretation and requires dedicated read-outs with consideration of underlying technical aspects.
format	article
author	Annelies Van Hemelryk Lisanne Mout Sigrun Erkens-Schulze Pim J. French Wytske M. van Weerden Martin E. van Royen
author_facet	Annelies Van Hemelryk Lisanne Mout Sigrun Erkens-Schulze Pim J. French Wytske M. van Weerden Martin E. van Royen
author_sort	Annelies Van Hemelryk
title	Modeling Prostate Cancer Treatment Responses in the Organoid Era: 3D Environment Impacts Drug Testing
title_short	Modeling Prostate Cancer Treatment Responses in the Organoid Era: 3D Environment Impacts Drug Testing
title_full	Modeling Prostate Cancer Treatment Responses in the Organoid Era: 3D Environment Impacts Drug Testing
title_fullStr	Modeling Prostate Cancer Treatment Responses in the Organoid Era: 3D Environment Impacts Drug Testing
title_full_unstemmed	Modeling Prostate Cancer Treatment Responses in the Organoid Era: 3D Environment Impacts Drug Testing
title_sort	modeling prostate cancer treatment responses in the organoid era: 3d environment impacts drug testing
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/721bef334d5b4664922d111ed7466a0c
work_keys_str_mv	AT anneliesvanhemelryk modelingprostatecancertreatmentresponsesintheorganoidera3denvironmentimpactsdrugtesting AT lisannemout modelingprostatecancertreatmentresponsesintheorganoidera3denvironmentimpactsdrugtesting AT sigrunerkensschulze modelingprostatecancertreatmentresponsesintheorganoidera3denvironmentimpactsdrugtesting AT pimjfrench modelingprostatecancertreatmentresponsesintheorganoidera3denvironmentimpactsdrugtesting AT wytskemvanweerden modelingprostatecancertreatmentresponsesintheorganoidera3denvironmentimpactsdrugtesting AT martinevanroyen modelingprostatecancertreatmentresponsesintheorganoidera3denvironmentimpactsdrugtesting
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Modeling Prostate Cancer Treatment Responses in the Organoid Era: 3D Environment Impacts Drug Testing

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