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