Abstract:
: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.
journal_name
Biomaterialsjournal_title
Biomaterialsauthors
Landberg G,Fitzpatrick P,Isakson P,Jonasson E,Karlsson J,Larsson E,Svanström A,Rafnsdottir S,Persson E,Gustafsson A,Andersson D,Rosendahl J,Petronis S,Ranji P,Gregersson P,Magnusson Y,Håkansson J,Ståhlberg Adoi
10.1016/j.biomaterials.2019.119705subject
Has Abstractpub_date
2020-03-01 00:00:00pages
119705eissn
0142-9612issn
1878-5905pii
S0142-9612(19)30823-3journal_volume
235pub_type
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