Abstract 36: A patient-centered approach to 3D <i>in vitro</i> modeling of pancreatic ductal adenocarcinoma

Abstract Matrigel® is the most commonly used hydrogel product for developing and testing 3-D in vitro pancreatic ductal adenocarcinoma (PDAC) models; however, its composition is not reflective of the ECM content of most PDAC tumors. To remedy this pitfall, we have developed a novel approach for generating patient-derived 3D tumor organoids grown in customized hydrogels that better reflect their original tumor tissue. Using surgically resected original patient tissue, we measured the relative area covered by the major ECM constituents in PDAC: collagens I, III, IV, and laminin via IHC. Cells collected from PDX-propagated patient tissues were then embedded in the custom hydrogel comprised of ECM proteins in concentration that mirrored the original patient tissue. Organoids will then be monitored for size and rate of proliferation via MTT assay. Finally, to ensure transmembrane interactions with the customized hydrogel, expression of integrins α1, α2, α6, which bind the aforementioned hydrogel components, will be measured via IHC. We anticipate organoids grown in these custom hydrogels will demonstrate a greater likelihood of successful model development and higher growth rate than those grown in Matrigel®. Additionally, we expect organoids grown by this method will show increased expression of integrins α1, α2, and α6. These results provide preliminary evidence that the composition of the hydrogel used to generate 3D in vitro models may have an impact on their phenotypic expression. Further development and characterization of these models could result in better reflection of in vivo conditions in preclinical therapy testing. Citation Format: Jade Vipond Cotter, Katie Reind. A patient-centered approach to 3D in vitro modeling of pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 36.