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dc.contributor.authorXu, Xian
Gurski, Lisa A.
Zhang, Chu
Harrington, Daniel A.
Farach-Carson, Mary C.
Jia, Xinqiao
dc.date.accessioned 2017-08-01T16:30:11Z
dc.date.available 2017-08-01T16:30:11Z
dc.date.issued 2012
dc.identifier.citation Xu, Xian, Gurski, Lisa A., Zhang, Chu, et al.. "Recreating the tumor microenvironment in a bilayer, hyaluronic acid hydrogel construct for the growth of prostate cancer spheroids." Biomaterials, 33, no. 35 (2012) Elsevier: 9049-9060. https://doi.org/10.1016/j.biomaterials.2012.08.061.
dc.identifier.urihttps://hdl.handle.net/1911/96012
dc.description.abstract Cancer cells cultured in physiologically relevant, three-dimensional (3D) matrices can recapture many essential features of native tumor tissues. In this study, a hyaluronic acid (HA)-based bilayer hydrogel system that not only supports the tumoroid formation from LNCaP prostate cancer (PCa) cells, but also simulates their reciprocal interactions with the tumor-associated stroma was developed and characterized. HA hydrogels were prepared by mixing solutions of HA precursors functionalized with acrylate groups (HA-AC) and reactive thiols (HA-SH) under physiological conditions. The resultant viscoelastic gels have an average elastic modulus of 234 ± 30 Pa and can be degraded readily by hyaluronidase. The orthogonal and cytocompatible nature of the crosslinking chemistry permits facile incorporation of cytokine-releasing particles and PCa cells. In our bilayer hydrogel construct, the top layer contains heparin (HP)-decorated, HA-based hydrogel particles (HGPs) capable of releasing heparin-binding epidermal growth factor-like growth factor (HB-EGF) in a sustained manner at a rate of 2.5 wt%/day cumulatively. LNCaP cells embedded in the bottom layer receive the growth factor signals from the top, and in response form enlarging tumoroids with an average diameter of 85 μm by day 7. Cells in 3D hydrogels assemble into spherical tumoroids, form close cellular contacts through E-cadherin, and show cortical organization of F-actin, whereas those plated as 2D monolayers adopt a spread-out morphology. Compared to cells cultured on 2D, the engineered tumoroids significantly increased the expression of two pro-angiogenic factors, vascular endothelial growth factor-165 (VEGF(165)) and interleukin-8 (IL-8), both at mRNA and protein levels. Overall, the HA model system provides a useful platform for the study of tumor cell responses to growth factors and for screening of anticancer drugs targeting these pathways.
dc.language.iso eng
dc.publisher Elsevier
dc.rights This is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by Elsevier.
dc.title Recreating the tumor microenvironment in a bilayer, hyaluronic acid hydrogel construct for the growth of prostate cancer spheroids
dc.type Journal article
dc.citation.journalTitle Biomaterials
dc.citation.volumeNumber 33
dc.citation.issueNumber 35
dc.identifier.digital Recreating_tumor_microenvironment
dc.type.dcmi Text
dc.identifier.doihttps://doi.org/10.1016/j.biomaterials.2012.08.061
dc.identifier.pmcid PMC3466381
dc.identifier.pmid 22999468
dc.type.publication post-print
dc.citation.firstpage 9049
dc.citation.lastpage 9060


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