Abstract 284: A 3D multicellular in vitro prostate cancer model featuring racially/ethnically diverse PDXs

Abstract

Abstract Current in vitro prostate cancer (PCa) research tools do not incorporate the complexities of the tumor microenvironment including perfusion, multiple cell types, extracellular matrix (ECM) and 3D-orientation. Additionally, these models lack racial/ethnic (R/E) diversity, failing to address the cancer health disparity (CHD) observed in Black men with PCa who experience double the incidence and mortality rates as compared to White men. Population-based in vitro PCa models that support crosstalk between different cell types will improve our understanding of the underlying mechanisms contributing to this CHD and improve the prediction of drug response in specific populations. Here, we used the high-throughput, perfusion-based microfluidic platform called the MIMETAS OrganoPlate® to culture up to 96 individual, multicellular PCa-on-a-chip cultures in parallel. PCa PDX cells of various R/E were embedded together with E2Crimson-labeled stromal fibroblasts in a migration-permissive hyaluronic acid hydrogel in the gel compartment, alongside an endothelium-lined perfusion channel containing a targeted immune cell population. Using high content imaging, we confirmed the stability and viability of the cultures over 7 days. The cultures maintained a 3D structure with PCa cells and fibroblasts evenly dispersed throughout the height of the gel compartment and a blood vessel-like structure within the perfusion channel. Closer evaluation of the gel compartment revealed a close association between PCa cells and stromal fibroblasts in a core-shell structure with PCa clusters surrounded by fibroblasts. Further, all cells maintained expected expression of phenotypic markers (PCa: epCAM, PSMA; fibroblast: vimentin, endothelium: CD31). For the immune component, medium and cell tracker dye conditions were optimized to support immune cell viability. Over 72 hours, immune cells were monitored, revealing migration of PBMCs through the gel compartment. Finally, the value of the complex, population-based multicellular in vitro model of PCa will be evaluated in a drug screen comparing the system with simple, PCa PDX monocultures. This R/E diverse 3D prostate tumor model will enable the full incorporation of all cell types and ECM into a single model which will better recapitulate population specific PCa and drug response. Citation Format: Divya Iyer, Andrei Bonteanu, Peter Shepherd, Rick Kittles, Nora Navone, Daniel Harrington, Kristin Bircsak. A 3D multicellular in vitro prostate cancer model featuring racially/ethnically diverse PDXs [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 284.