Benchmarking to the Gold Standard Hyaluronan-Oxime Hydrogels Recapitulate Xenograft Models with In Vitro Breast Cancer Spheroid Culture

Benchmarking to the Gold Standard : Hyaluronan-Oxime Hydrogels Recapitulate Xenograft Models with In Vitro Breast Cancer Spheroid Culture

© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Bibliographische Detailangaben
Veröffentlicht in:Advanced materials (Deerfield Beach, Fla.). - 1998. - 31(2019), 36 vom: 19. Sept., Seite e1901166
1. Verfasser: Baker, Alexander E G (VerfasserIn)
Weitere Verfasser: Bahlmann, Laura C, Tam, Roger Y, Liu, Jeffrey C, Ganesh, Ahil N, Mitrousis, Nikolaos, Marcellus, Richard, Spears, Melanie, Bartlett, John M S, Cescon, David W, Bader, Gary D, Shoichet, Molly S
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2019
Zugriff auf das übergeordnete Werk:Advanced materials (Deerfield Beach, Fla.)
Schlagworte:Journal Article 3D cell culture breast cancer drug screening hyaluronic acid hydrogels Hydrogels Oximes Hyaluronic Acid 9004-61-9
Beschreibung
Zusammenfassung:© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Many 3D in vitro models induce breast cancer spheroid formation; however, this alone does not recapitulate the complex in vivo phenotype. To effectively screen therapeutics, it is urgently needed to validate in vitro cancer spheroid models against the gold standard of xenografts. A new oxime-crosslinked hyaluronan (HA) hydrogel is designed, manipulating gelation rate and mechanical properties to grow breast cancer spheroids in 3D. This HA-oxime breast cancer model maintains the gene expression profile most similar to that of tumor xenografts based on a pan-cancer gene expression profile (comprising 730 genes) of three different human breast cancer subtypes compared to Matrigel or conventional 2D culture. Differences in gene expression between breast cancer cultures in HA-oxime versus Matrigel or 2D are confirmed for 12 canonical pathways by gene set variation analysis. Importantly, drug response is dependent on the culture method. Breast cancer cells respond better to the Rac inhibitor (EHT-1864) and the PI3K inhibitor (AZD6482) when cultured in HA-oxime versus Matrigel. This study demonstrates the superiority of an HA-based hydrogel as a platform for in vitro breast cancer culture of both primary, patient-derived cells and cell lines, and provides a hydrogel culture model that closely matches that in vivo
Beschreibung:Date Completed 16.01.2020
Date Revised 30.09.2020
published: Print-Electronic
Citation Status MEDLINE
ISSN:1521-4095
DOI:10.1002/adma.201901166