IBCN 2020: Development and Characterization of a Novel Autochthonous Semi-Spontaneous Bladder Cancer Model By Pathological Evaluation, Single Cell Sequencing and Proteomic Profiling

(UroToday.com) Dr. Kerzeli presented work by her and colleagues from Uppsala University, Sweden, where they induced and profiled an autochthonous bladder cancer model in an effort to improve understanding of bladder tumor development and progression in the native microenvironment.

Oral carcinogens were administered to Hgf-Cdk4R24C mice, and genomic, proteomic, and histopathologic analyses were performed on the resulting bladder tumors. The carcinogen exposure led to the development of non-muscle invasive bladder tumors that differed from exposed wild-type C57BL/6 mice, while females developed T1 tumors faster than males. Tumors were of Tis/T1 stage with squamous differentiation and progressed to muscle-invasive disease within 10 weeks. Single-cell sequencing demonstrated three predominant molecular clusters with distinct profiles trending towards the luminal or basal subtype and genomic instability. Carcinogen-induced bladders showed a clear change in neutrophil, macrophage, and fibroblast populations.

Therapeutic studies performed at the non-muscle invasive stage with anti-PD1 did not prevent progression, although a possible delay in tumor growth was seen in females. A cell line was derived from an outgrown Hgf-Cdk4R24Csubcutaneous tumor, which showed susceptibility to CpG ODN treatment in female mice (Figure).

Figure: New cell lines and from autochthonous Hgf-Cdk4R24C urothelial tumors, and their susceptibility.

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Presented by: Iliana K. Kerzeli, Ph.D., Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.


 
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