Muraro, Manuele Giuseppe. Functional validation of cancer stem cell markers in primary human colorectal cancer and established cell lines. 2014, PhD Thesis, University of Basel, Faculty of Science.
Official URL: http://edoc.unibas.ch/diss/DissB_11064
In this work, I addressed a) the prognostic relevance of the expression of CSC surface markers in CRC clinical specimens, b) the “in vivo” tumorigenicity of primary CRC derived cells, as related to their expression of putative CSC surface markers, c) the possibility of using cells derived from established CRC cell lines expressing CSC surface markers as CSC cellular model, and finally d) the development of innovative culture models of potential relevance for the screening of anti CRC compounds.
I have analyzed the surface markers expression in correlation with stem cell-like functional features, but no consistent results was found confirming stemness property associated with expression of those markers. These results obviously question the validity of putative surface CRC-SC markers. Taken together these data might suggest that their expression and CSC functional features might be associated with some degree of plasticity, potentially related to tumor microenvironmental characteristics being lost in conventionally cultured tumor cell lines and in primary tumor derived cell suspensions.
Based on this background I have investigated the possibility to perform 3D culture of CRC cell lines to assess whether these systems might provide useful insights for the interpretation of our data. My findings clearly document the plasticity of gene expression profiles of cultured CRC cells depending on their three-dimensional architectures. Most importantly, I demonstrate that major gene expression modulation events only occur when culture in 3D spheroids is associated with ischemia and necrosis. I also showed that the gene expression of putative CSC markers increases with the occurrence of ischemia and necrosis in the core of a 3D spheroid.
|Advisors:||Spagnoli, Giulio C.|
|Committee Members:||Christofori, Gerhard M.|
|Faculties and Departments:||03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Oncology Surgery (Spagnoli/Heberer)|
|Bibsysno:||Link to catalogue|
|Number of Pages:||97 S.|
|Last Modified:||30 Jun 2016 10:56|
|Deposited On:||05 Jan 2015 15:25|
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