Ratiometric Inclusion of Fibroblasts Promotes Both Castration-Resistant and Androgen-Dependent Tumorigenic Progression in Engineered Prostate Cancer Tissues.

Autor: Habbit NL; Department of Chemical Engineering, Samuel Ginn College of Engineering, Auburn University, 212 Ross Hall, Auburn, AL, 36849, USA., Anbiah B; Department of Chemical Engineering, Samuel Ginn College of Engineering, Auburn University, 212 Ross Hall, Auburn, AL, 36849, USA., Suresh J; Department of Chemical Engineering, Samuel Ginn College of Engineering, Auburn University, 212 Ross Hall, Auburn, AL, 36849, USA., Anderson L; Department of Chemical Engineering, Samuel Ginn College of Engineering, Auburn University, 212 Ross Hall, Auburn, AL, 36849, USA., Davies ML; Department of Chemical Engineering, Samuel Ginn College of Engineering, Auburn University, 212 Ross Hall, Auburn, AL, 36849, USA., Hassani I; Department of Chemical Engineering, Samuel Ginn College of Engineering, Auburn University, 212 Ross Hall, Auburn, AL, 36849, USA., Ghosh TM; Department of Drug Discovery and Development, Harrison College of Pharmacy, Auburn University, 720 So. Donahue Dr., Pharmaceutical Research Building, Auburn, AL, 36849, USA., Greene MW; Department of Nutritional Sciences, College of Human Sciences, Auburn University, 210 Spidle Hall, Auburn, AL, 36849, USA., Prabhakarpandian B; Biomedical Technology Division, CFD Research Corporation, 701 McMillian Way NW, Huntsville, AL, 35806, USA., Arnold RD; Department of Drug Discovery and Development, Harrison College of Pharmacy, Auburn University, 720 So. Donahue Dr., Pharmaceutical Research Building, Auburn, AL, 36849, USA., Lipke EA; Department of Chemical Engineering, Samuel Ginn College of Engineering, Auburn University, 212 Ross Hall, Auburn, AL, 36849, USA.
Jazyk: angličtina
Zdroj: Advanced healthcare materials [Adv Healthc Mater] 2023 Dec; Vol. 12 (32), pp. e2301139. Date of Electronic Publication: 2023 Oct 31.
DOI: 10.1002/adhm.202301139
Abstrakt: To investigate the ratiometric role of fibroblasts in prostate cancer (PCa) progression, this work establishes a matrix-inclusive, 3D engineered prostate cancer tissue (EPCaT) model that enables direct coculture of neuroendocrine-variant castration-resistant (CPRC-ne) or androgen-dependent (ADPC) PCa cells with tumor-supporting stromal cell types. Results show that the inclusion of fibroblasts within CRPC-ne and ADPC EPCaTs drives PCa aggression through significant matrix remodeling and increased proliferative cell populations. Interestingly, this is observed to a much greater degree in EPCaTs formed with a small number of fibroblasts relative to the number of PCa cells. Fibroblast coculture also results in ADPC behavior more similar to the aggressive CRPC-ne condition, suggesting fibroblasts play a role in elevating PCa disease state and may contribute to the ADPC to CRPC-ne switch. Bulk transcriptomic analyses additionally elucidate fibroblast-driven enrichment of hallmark gene sets associated with tumorigenic progression. Finally, the EPCaT model clinical relevancy is probed through a comparison to the Cancer Genome Atlas (TCGA) PCa patient cohort; notably, similar gene set enrichment is observed between EPCaT models and the patient primary tumor transcriptome. Taken together, study results demonstrate the potential of the EPCaT model to serve as a PCa-mimetic tool in future therapeutic development efforts.
(© 2023 Wiley-VCH GmbH.)
Databáze: MEDLINE
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