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dc.contributor.authorFong, Eliza L.S.
Wan, Xinhai
Yang, Jun
Morgado, Micaela
Mikos, Antonios G.
Harrington, Daniel A.
Navone, Nora M.
Farach-Carson, Mary C.
dc.date.accessioned 2017-05-22T21:48:43Z
dc.date.available 2017-05-22T21:48:43Z
dc.date.issued 2016
dc.identifier.citation Fong, Eliza L.S., Wan, Xinhai, Yang, Jun, et al.. "A 3D inᅠvitro model of patient-derived prostate cancer xenograft for controlled interrogation of inᅠvivo tumor-stromal interactions." Biomaterials, 77, (2016) Elsevier: 164-172. https://doi.org/10.1016/j.biomaterials.2015.10.059.
dc.identifier.urihttps://hdl.handle.net/1911/94340
dc.description.abstract Patient-derived xenograft (PDX) models better represent human cancer than traditional cell lines. However, the complex in vivo environment makes it challenging to employ PDX models to investigate tumor-stromal interactions, such as those that mediate prostate cancer (PCa) bone metastasis. Thus, we engineered a defined three-dimensional (3D) hydrogel system capable of supporting the co-culture of PCa PDX cells and osteoblastic cells to recapitulate the PCa-osteoblast unit within the bone metastatic microenvironment in vitro. Our 3D model not only maintained cell viability but also preserved the typical osteogenic phenotype of PCa PDX cells. Additionally, co-culture cellularity was maintained over that of either cell type cultured alone, suggesting that the PCa-osteoblast cross-talk supports PCa progression in bone, as is hypothesized to occur in patients with prostatic bone metastasis. Strikingly, osteoblastic cells co-cultured with PCa PDX tumoroids organized around the tumoroids, closely mimicking the architecture of PCa metastases in bone. Finally, tumor-stromal signaling mediated by the fibroblast growth factor axis tightly paralleled that in the in vivo counterpart. Together, these findings indicate that this 3D PCa PDX model recapitulates important pathological properties of PCa bone metastasis, and validate the use of this model for controlled and systematic interrogation of complex in vivo tumor-stromal interactions.
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 A 3D inᅠvitro model of patient-derived prostate cancer xenograft for controlled interrogation of inᅠvivo tumor-stromal interactions
dc.type Journal article
dc.citation.journalTitle Biomaterials
dc.subject.keywordco-culture
hydrogel
model
osteoblasts
patient-derived xenograft
prostate cancer
three-dimensional
dc.citation.volumeNumber 77
dc.type.dcmi Text
dc.identifier.doihttps://doi.org/10.1016/j.biomaterials.2015.10.059
dc.identifier.pmcid PMC4684431
dc.identifier.pmid 26599623
dc.type.publication post-print
dc.citation.firstpage 164
dc.citation.lastpage 172


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