184P - Alterations in tumorigenicity and immunogenicity of bladder cancer cells after somatic cell reprogramming

Background

Somatic cell reprogramming results in generation of induced pluripotent stem cells (iPSCs) which demonstrate similar gene expression, morphology, epigenetic profile and three-germ layer differentiation capacity to those of embryonic stem cells. Therefore patient-derived iPSCs can act as a powerful tool both for understanding disease mechanism and for regenerative medicine. Cancer cell reprogramming offers a unique model to study tumor initiation and progression as well as to create patient-specific cancer models for toxicity screening and developing personalised therapeutic strategies. Here, we primarily focused on reprogramming grade 4 bladder cancer cell lines to identify potential biomarkers for early cancer detection and cancer immunotherapy.

Methods

Grade 4 bladder cancer cells were transduced with a non-genome integrating Sendai virus system carrying Yamanaka factors Oct3/4, Sox2, Klf4, and c-Myc. Reprogrammed bladder cancer cells were cultured in a feeder-free iPSC system. Pluripotency-associated features were characterised using functional assays, immunofluorescence and western blotting. The nano HPLC LC-MS/MS system was utilised for comprehensive proteome analysis, followed by protein-protein interaction network analysis via STRING.

Results

Reprogrammed bladder cancer cells expressed pluripotency-associated factors, changed cell morphology and motility. Proteomic analysis showed a decrease in the proteins related to the immune system process. Protein-protein interaction network analysis highlighted key proteins involved in antigen processing and presentation of endogeneous peptide antigen via MHC class I and interleukin-27-mediated signaling pathway.

Conclusions

After somatic cell reprogramming, ancestral cancer cells shift from malignancy to benignity in their proteome, affecting various cellular processes including immune system function, stem cell maintenance, differentiation, apoptosis, cell adhesion, and motility. Major changes were observed in the proteins of the immune system, indicating that the unique immunogenicity of cancer cell-derived iPS cells could be used in targeted therapies and potential drug design.

Legal entity responsible for the study

Banu Iskender Izgi.

Funding

Health Institutes of Türkiye (TUSEB).

Disclosure

All authors have declared no conflicts of interest.