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Wimmers, D.G.* ; Huebner, K.* ; Dale, T.* ; Papargyriou, A. ; Reichert, M. ; Hartmann, A.* ; Schneider-Stock, R.*

A floating collagen matrix triggers ring formation and stemness characteristics in human colorectal cancer organoids.

Pathol. Res. Pract. 269:155890 (2025)

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	Open Access Gold (Paid Option)

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Intestinal organoids reflect the 3D structure and function of their original tissues. Organoid are typically cultured in Matrigel, an extracellular matrix (ECM) mimicking the basement membrane, which is suitable for epithelial cells but does not accurately mimic the tumour microenvironment of colorectal cancer (CRC). The ECM and particularly collagen type I is crucial for CRC progression and invasiveness. Given that efforts to examine CRC organoid invasion in a more physiologically relevant ECM have been limited, we used a floating collagen type I matrix (FC) to study organoid invasion in three patient-derived CRC organoid lines. In FC gel, organoids contract, align, and fuse into macroscopic ring structures, initiating minor branch formation and invasion fronts, phenomena unique for the collagen ECM and otherwise not observed in Matrigel-grown CRC organoids. In contrast to Matrigel, FC organoids showed basal extrusion with improper actin localization, but without change in the organoid polarity. Moreover, small clusters of vital invading cells were observed. Gene expression analysis revealed that the organoids cultured in a FC matrix presented more epithelial and stem cell-like characteristics. This novel technique of cultivating CRC organoids in a FC matrix represents an in-vitro model for studying cancer organization and matrix remodelling with increased organoid stemness potential.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Collagen I ; Invasiveness ; Matrigel ; Ring Structures ; Stemness ; Trop2; Invasion

ISSN (print) / ISBN 0344-0338

e-ISSN 1618-0631

Journal Pathology, Research and Practice

Quellenangaben Volume: 269, Article Number: 155890

Publisher Urban & Fischer

Publishing Place Hackerbrucke 6, 80335 Munich, Germany

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Stem Cell Research (ISF)

Grants BZKF Lighthouse Project "Preclinical Model Systems"
Bayerisch-Tschechische Hochschulagentur
German Research Foundation (Deutsche Forschungsgemeinschaft)
Federal Ministry of Education and Research (BMBF)
Project SATURN3
Project QuE-MRT
Project FAIRPACT
DKTK (German Consortium for Translational Cancer Research) Strategic Initiative Organoid Platform
Bavarian Cancer Research Center (BZKF) Translational Group "SARIFA T3riangle"
Deutsche Forschungsgemeinschaft