To investigate the ratiometric role of fibroblasts in prostate cancer (PCa) progression, this work establishes a matrix‐inclusive, three‐dimensional 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.This article is protected by copyright. All rights reserved
Crossbred heifers (n = 64; animal was the experimental unit) were assigned to 1 of 8 treatments in a 4 × 2 factorial arrangement, with 4 treatment days-on-feed (DOF; 79, 100, 121, 142) and 2 levels of ractopamine hydrochloride (RAC) supplementation (0 or 300 mg × hd–1 × d–1). At 24 h postmortem, carcass traits were determined by trained personnel and longissimus samples were removed for muscle fiber type analyses. Boneless strip loins (IMPS #180) were fabricated and vacuum-packaged at 24 h postmortem and aged for 21 d, cut into 2.54 cm thick steaks, then frozen for no longer than 6 mo. After thawing for 24 h, Warner-Bratzler shear force (WBSF) and trained sensory panel analyses were conducted. Marbling was greater (P < 0.05) for control (CON; 0 mg x hd-1 x d-1 ractopamine hydrochloride) heifers than RAC heifers fed for either 79 or 100 d, but lower (P < 0.05) for CON heifers than RAC heifers fed for either 121 or 142 DOF. Feeding RAC had no effect (P > 0.05) on carcass traits, muscle fiber histology, or meat quality. The addition of RAC had no effect (P > 0.05) on Warner-Bratzler shear force. Feeding RAC had no negative impacts on carcass traits or meat quality and actually improved marbling scores in longer-fed heifers.
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