A human-derived prostate co-culture microtissue model using epithelial (RWPE-1) and stromal (WPMY-1) cell lines. (October 2019)

• Record Type: Journal Article
• Authors: Dent, Matthew P.; Madnick, Samantha J.; Hall, Susan; Vantangoli Policelli, Marguerite; Bars, Chloe; Li, Hui; Amin, Ali; Carmichael, Paul L.; Martin, Francis L.; Boekelheide, Kim
• Is Part Of: Toxicology in vitro. Volume 60(2019)
• Page Start: 203
• Page End: 211
• Publication Date: 2019-10
• Subjects: Toxicity testing -- In vitro -- Periodicals; Toxicology -- Periodicals; 615.9
• DOI: 10.1016/j.tiv.2019.05.023
• Languages: English
• ISSNs: 0887-2333

Abstract

Abstract: The development and normal function of prostate tissue depends on signalling interactions between stromal and epithelial compartments. Development of a prostate microtissue composed of these two components can help identify substance exposures that could cause adverse effects in humans as part of a non-animal risk assessment. In this study, prostate microtissues composed of human derived stromal (WPMY-1) and epithelial (RWPE-1) cell lines grown in scaffold-free hydrogels were developed and characterized using immunohistochemistry, light microscopy, and qRT-PCR. Within 5 days after seeding, the microtissues self-organized into spheroids consisting of a core of stromal WPMY-1 cells surrounded by epithelial RWPE-1 cells. The RWPE-1 layer is reflective of intermediate prostatic epithelium, expressing both characteristics of the luminal (high expression of PSA) and basal (high expression of cytokeratins 5/6 and 14) epithelial cells. The response of the microtissues to an androgen (dihydrotestosterone, DHT) and an anti-androgen (flutamide) was also investigated. Treatment with DHT, flutamide or a mixture of DHT and flutamide indicated that the morphology and self-organization of the microtissues is androgen dependent. qRT-PCR data showed that a saturating concentration of DHT increased the expression of genes coding for the estrogen receptors ( ESR1 and ESR2 ) and decreased the expression of CYP1B1 without affecting the expression of the androgen receptor. With further development and optimization RWPE-1/WPMY-1 microtissues can play an important role in non-animal risk assessments. Highlights: Non-animal risk assessment requires innovative cellular models representative of human biology. RWPE-1 and WPMY-1 cells form microtissues when grown in scaffold-free hydrogels. Microtissues represent an early stage of human prostate development. Morphological and molecular biomarkers are responsive to androgens/anti-androgens.