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Patient-derived scaffolds uncover breast cancer promoting properties of the microenvironment
University of Gothenburg, Sweden.
University of Gothenburg, Sweden.
University of Gothenburg, Sweden.
University of Gothenburg, Sweden.
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2020 (English)In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 235, article id 119705Article in journal (Refereed) Published
Abstract [en]

Tumor cells interact with the microenvironment that specifically supports and promotes tumor development. Key components in the tumor environment have been linked to various aggressive cancer features and can further influence the presence of subpopulations of cancer cells with specific functions, including cancer stem cells and migratory cells. To model and further understand the influence of specific microenvironments we have developed an experimental platform using cell-free patient-derived scaffolds (PDSs) from primary breast cancers infiltrated with standardized breast cancer cell lines. This PDS culture system induced a series of orchestrated changes in differentiation, epithelial-mesenchymal transition, stemness and proliferation of the cancer cell population, where an increased cancer stem cell pool was confirmed using functional assays. Furthermore, global gene expression profiling showed that PDS cultures were similar to xenograft cultures. Mass spectrometry analyses of cell-free PDSs identified subgroups based on their protein composition that were linked to clinical properties, including tumor grade. Finally, we observed that an induction of epithelial-mesenchymal transition-related genes in cancer cells growing on the PDSs were significantly associated with clinical disease recurrences in breast cancer patients. Patient-derived scaffolds thus mimics in vivo-like growth conditions and uncovers unique information about the malignancy-inducing properties of tumor microenvironment. © 2019 The Authors

Place, publisher, year, edition, pages
Elsevier Ltd , 2020. Vol. 235, article id 119705
Keywords [en]
Breast cancer, Cancer stem cells, Differentiation, Infiltration, Malignancy, Scaffold, Cell culture, Cell proliferation, Differentiation (calculus), Diseases, Gene expression, Mass spectrometry, Scaffolds, Stem cells, Tumors, Epithelial-mesenchymal transition, Experimental platform, Gene expression profiling, Mass spectrometry analysis, Tumor microenvironment, Scaffolds (biology)
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Natural Sciences
Identifiers
URN: urn:nbn:se:ri:diva-43392DOI: 10.1016/j.biomaterials.2019.119705Scopus ID: 2-s2.0-85077985377OAI: oai:DiVA.org:ri-43392DiVA, id: diva2:1390365
Note

Funding details: Västra Götalandsregionen; Funding details: Barncancerfonden, 2017-0043; Funding details: Vetenskapsrådet, VR, 2016-01530, 2017-01392; Funding details: VINNOVA, 2017-03737; Funding details: Stiftelsen för Strategisk Forskning, SSF; Funding details: Swedish Cancer Foundation, 2016-438, 2016-486, PjF 20 0306; Funding details: Knut och Alice Wallenbergs Stiftelse; Funding details: American Liver Foundation, ALF, 721091, 716321; Funding details: Göteborgs Universitet; Funding details: Stiftelsen Assar Gabrielssons Fond, AG Fond; Funding text 1: We thank the people at Departments of Pathology and Surgery, Sahlgrenska University Hospital for technical assistance handling breast cancer samples and Gothenburg University Proteomics Core Facility for their support. This work was supported by grants from Assar Gabrielssons Research Foundation ; BioCARE National Strategic Research Program at University of Gothenburg; Johan Jansson Foundation for Cancer Research; Knut and Alice Wallenberg Foundation, Wallenberg Center for Molecular and Translational Medicine, University of Gothenburg, Sweden; Region Västra Götaland; Swedish Cancer Foundation (PjF 20 0306 , 2016-438 and 2016-486 ); Swedish Foundation for Strategic Research ; Swedish Research Council ( 2017-01392 and 2016-01530 ); Swedish Childhood Cancer Foundation ( 2017-0043) ; the Swedish state under the agreement between the Swedish government and the county councils, the ALF agreement ( 716321 and 721091 ); Wilhelm and Martina Lundgren Foundation for Scientific Research and VINNOVA ( 2017-03737 ). Appendix A

Available from: 2020-01-31 Created: 2020-01-31 Last updated: 2020-01-31Bibliographically approved

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Petronis, SarunasHåkansson, Joakim

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