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Patient-derived scaffolds as a model of colorectal cancer
University of Gothenburg, Sweden.
University of Gothenburg, Sweden.
University of Gothenburg, Sweden.
RISE Research Institutes of Sweden, Materials and Production, Chemistry, Biomaterials and Textiles. University of Gothenburg, Sweden.ORCID iD: 0000-0002-4270-8475
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2021 (English)In: Cancer Medicine, E-ISSN 2045-7634, Vol. 10, no 3, p. 867-882Article in journal (Refereed) Published
Abstract [en]

Background: Colorectal cancer is the second most common cause of cancer-related death worldwide and standardized therapies often fail to treat the more aggressive and progressive types of colorectal cancer. Tumor cell heterogeneity and influence from the surrounding tumor microenvironment (TME) contribute to the complexity of the disease and large variability in clinical outcomes. Methods: To model the heterogeneous nature of colorectal cancer, we used patient-derived scaffolds (PDS), which were obtained via decellularization of surgically resected tumor material, as a growth substrate for standardized cell lines. Results: After confirmation of native cell absence and validation of the structural and compositional integrity of the matrix, 89 colorectal PDS were repopulated with colon cancer cell line HT29. After 3 weeks of PDS culture, HT29 cells varied their gene and protein expression profiles considerably compared to 2D-grown HT29 cells. Markers associated with proliferation were consistently decreased, while markers associated with pluripotency were increased in PDS-grown cells compared to their 2D counterparts. When comparing the PDS-induced changes in HT29 cells with clinically relevant tumor information from individual patients, we observed significant associations between stemness/pluripotency markers and tumor location, and between epithelial-to-mesenchymal transition (EMT) markers and cancer mortality. Kaplan–Meier analysis revealed that low PDS-induced EMT correlated with worse cancer-specific survival. Conclusions: The colorectal PDS model can be used as a simplified personalized tool that can potentially reveal important diagnostic and pathophysiological information related to the TME. © 2020 The Authors.

Place, publisher, year, edition, pages
Blackwell Publishing Ltd , 2021. Vol. 10, no 3, p. 867-882
Keywords [en]
cancer stem cells, colorectal cancer, decellularized matrix, infiltration, malignancy, patient-derived scaffold, scaffold
National Category
Natural Sciences
Identifiers
URN: urn:nbn:se:ri:diva-51485DOI: 10.1002/cam4.3668Scopus ID: 2-s2.0-85097923252OAI: oai:DiVA.org:ri-51485DiVA, id: diva2:1516295
Note

 Funding details: Västra Götalandsregionen, 2019‐01273; Funding details: 721091, 716321, 784211, 2019‐0317; Funding details: VINNOVA, 2017‐03737; Funding details: Vetenskapsrådet, VR, 2016‐01530, 2017‐01392; Funding details: Knut och Alice Wallenbergs Stiftelse; Funding details: Johan Jansson Foundation; Funding details: Cancerfonden, 19‐0306; Funding details: Wallenberg Centre for Molecular and Translational Medicine, WCMTM; Funding details: Stiftelsen Assar Gabrielssons Fond, AG Fond; Funding text 1: This research was funded by Assar Gabrielssons Research Foundation; Johan Jansson Foundation for Cancer Research; Knut and Alice Wallenberg Foundation, Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden; Swedish Cancer Society (19‐0306); Swedish Research Council (2016‐01530, 2017‐01392); the Swedish state under the agreement between the Swedish government and the county councils, the ALF‐agreement (716321, 721091, 784211); Wilhelm and Martina Lundgren Foundation for Scientific Research, Cancerfonden (2019‐0317), VINNOVA (2017‐03737), and Västra Götalandsregionen (2019‐01273).

Available from: 2021-01-11 Created: 2021-01-11 Last updated: 2024-01-17Bibliographically approved

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