Journal Article

DKFZ-2025-01253

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png A 3D patternoid model for the reproducible characterization of invasive phenotypes and drug sensitivity in PDAC.

Kurzbach, S. C. ; Carvajal-Heckele, V. ; Teshima, T. F. ; Reichert, M.DKFZ* ; Bausch, A. R.

2025
RSC Cambridge

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Please use a persistent id in citations: doi:10.1039/D5LC00203F

Abstract: Pancreatic ductal adenocarcinoma (PDAC) is a highly invasive and heterogeneous malignancy, posing challenges for reproducible modeling and functional phenotypic analysis. To address these limitations, we developed a standardized 3D patternoid platform using collagen-based microcavity arrays to enhance organoid formation consistency and quantify subtype-specific invasion mechanisms. We utilized murine primary PDAC cells stratified by epithelial-mesenchymal transition (EMT) into three subtypes: epithelial (E-9591), hybrid EMT (Mlow-8028), and mesenchymal (M-16992). The platform's sensitivity was verified by a strong correlation between EMT scores and invasive phenotypes, as well as responses to physiological concentrations of the protease inhibitor batimastat. Key invasion parameters-including invasive area, maximum invasion distance, and branching complexity-were measured under both genomic and drug-induced conditions. The platform demonstrated high inter-organoid reproducibility, with precise control over initial cell numbers ensuring batch-to-batch comparability. Invasion dynamics analysis revealed that epithelial cells (E-9591) primarily relied on spatial constraints within the microcavity to invade. Batimastat drug sensitivity assays further distinguished invasion dependencies of the mesenchymal subtypes, confirming that M-16992 patternoids exhibit a stronger sensitivity towards MMP inhibition compared to Mlow-8028 patternoids. Concurrentlty, both subtypes experienced a shift towards epithelial-like spatial constraint triggered invasion morphology, reflecting the plasticity of PDAC invasiveness. This scalable and adaptable 3D patternoid platform enables high-throughput analysis of invasive behaviors and therapeutic responses, offering significant potential for preclinical cancer research and personalized medicine.

Note: 2025 Jul 8;25(14):3411-3422

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Contributing Institute(s):

1. DKTK Koordinierungsstelle München (MU01)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2025

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Current Contents - Physical, Chemical and Earth Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; JCR ; National-Konsortium ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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