Patient-derived scaffolds as a drug-testing platform for endocrine therapies in breast cancer

Abstract Three-dimensional cell culture platforms based on decellularised patient-based microenvironments provide in vivo-like growth conditions allowing cancer cells to interact with intact structures and components of the surrounding tissue. A patient-derived scaffold (PDS) model was therefore eva...

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Autores principales:	Anna Gustafsson, Elena Garre, Maria Carmen Leiva, Simona Salerno, Anders Ståhlberg, Göran Landberg
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c7aee6255bcd481eb4ae53bb386c2cb9
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spelling	oai:doaj.org-article:c7aee6255bcd481eb4ae53bb386c2cb92021-12-02T17:12:17ZPatient-derived scaffolds as a drug-testing platform for endocrine therapies in breast cancer10.1038/s41598-021-92724-92045-2322https://doaj.org/article/c7aee6255bcd481eb4ae53bb386c2cb92021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-92724-9https://doaj.org/toc/2045-2322Abstract Three-dimensional cell culture platforms based on decellularised patient-based microenvironments provide in vivo-like growth conditions allowing cancer cells to interact with intact structures and components of the surrounding tissue. A patient-derived scaffold (PDS) model was therefore evaluated as a testing platform for the endocrine therapies (Z)-4-Hydroxytamoxifen (4OHT) and fulvestrant as well as the CDK4/6-inhibitor palbociclib, monitoring the treatment responses in breast cancer cell lines MCF7 and T47D adapted to the patient-based microenvironments. MCF7 cells growing in PDSs showed increased resistance to 4OHT and fulvestrant treatment (100- and 20-fold) compared to 2D cultures. Quantitative PCR analyses of endocrine treated cancer cells in PDSs revealed upregulation of pluripotency markers further supported by increased self-renewal capacity in sphere formation assays. When comparing different 3D growth platforms including PDS, matrigel, gelatin sponges and 3D-printed hydrogels, 3D based cultures showed slightly varying responses to fulvestrant and palbociclib whereas PDS and matrigel cultures showed more similar gene expression profiles for 4OHT treatment compared to the other platforms. The results support that the PDS technique maximized to provide a multitude of smaller functional PDS replicates from each primary breast cancer, is an up-scalable patient-derived drug-testing platform available for gene expression profiling and downstream functional assays.Anna GustafssonElena GarreMaria Carmen LeivaSimona SalernoAnders StåhlbergGöran LandbergNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Anna Gustafsson Elena Garre Maria Carmen Leiva Simona Salerno Anders Ståhlberg Göran Landberg Patient-derived scaffolds as a drug-testing platform for endocrine therapies in breast cancer
description	Abstract Three-dimensional cell culture platforms based on decellularised patient-based microenvironments provide in vivo-like growth conditions allowing cancer cells to interact with intact structures and components of the surrounding tissue. A patient-derived scaffold (PDS) model was therefore evaluated as a testing platform for the endocrine therapies (Z)-4-Hydroxytamoxifen (4OHT) and fulvestrant as well as the CDK4/6-inhibitor palbociclib, monitoring the treatment responses in breast cancer cell lines MCF7 and T47D adapted to the patient-based microenvironments. MCF7 cells growing in PDSs showed increased resistance to 4OHT and fulvestrant treatment (100- and 20-fold) compared to 2D cultures. Quantitative PCR analyses of endocrine treated cancer cells in PDSs revealed upregulation of pluripotency markers further supported by increased self-renewal capacity in sphere formation assays. When comparing different 3D growth platforms including PDS, matrigel, gelatin sponges and 3D-printed hydrogels, 3D based cultures showed slightly varying responses to fulvestrant and palbociclib whereas PDS and matrigel cultures showed more similar gene expression profiles for 4OHT treatment compared to the other platforms. The results support that the PDS technique maximized to provide a multitude of smaller functional PDS replicates from each primary breast cancer, is an up-scalable patient-derived drug-testing platform available for gene expression profiling and downstream functional assays.
format	article
author	Anna Gustafsson Elena Garre Maria Carmen Leiva Simona Salerno Anders Ståhlberg Göran Landberg
author_facet	Anna Gustafsson Elena Garre Maria Carmen Leiva Simona Salerno Anders Ståhlberg Göran Landberg
author_sort	Anna Gustafsson
title	Patient-derived scaffolds as a drug-testing platform for endocrine therapies in breast cancer
title_short	Patient-derived scaffolds as a drug-testing platform for endocrine therapies in breast cancer
title_full	Patient-derived scaffolds as a drug-testing platform for endocrine therapies in breast cancer
title_fullStr	Patient-derived scaffolds as a drug-testing platform for endocrine therapies in breast cancer
title_full_unstemmed	Patient-derived scaffolds as a drug-testing platform for endocrine therapies in breast cancer
title_sort	patient-derived scaffolds as a drug-testing platform for endocrine therapies in breast cancer
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/c7aee6255bcd481eb4ae53bb386c2cb9
work_keys_str_mv	AT annagustafsson patientderivedscaffoldsasadrugtestingplatformforendocrinetherapiesinbreastcancer AT elenagarre patientderivedscaffoldsasadrugtestingplatformforendocrinetherapiesinbreastcancer AT mariacarmenleiva patientderivedscaffoldsasadrugtestingplatformforendocrinetherapiesinbreastcancer AT simonasalerno patientderivedscaffoldsasadrugtestingplatformforendocrinetherapiesinbreastcancer AT andersstahlberg patientderivedscaffoldsasadrugtestingplatformforendocrinetherapiesinbreastcancer AT goranlandberg patientderivedscaffoldsasadrugtestingplatformforendocrinetherapiesinbreastcancer
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Patient-derived scaffolds as a drug-testing platform for endocrine therapies in breast cancer

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