Enrichment of genes associated with squamous differentiation in cancer initiating cells isolated from urothelial cells transformed by the environmental toxicant arsenite.

Arsenic is an environmental toxicant with long-term exposure associated with the development of urothelial carcinomas. Our lab has developed an in-vitro model of urothelial carcinoma by exposing the immortal, but non-tumorigenic bladder cell line, the UROtsa, to arsenite (As). These transformed cells form tumors in immune-compromised mice, which resemble urothelial carcinomas with components of the tumor exhibiting squamous differentiation.

The urothelial cell line UROtsa transformed by arsenite and cadmium display basal characteristics associated with muscle invasive urothelial cancers.

Muscle invasive urothelial carcinomas are divided into various molecular subtypes with basal and luminal subtypes being the prominent ones. The basal muscle-invasive urothelial carcinomas are generally more aggressive at presentation and significantly enriched with squamous features. Our laboratory has developed an in-vitro model of urothelial cancer by transforming the immortalized cell line UROtsa with arsenite (As3+) and cadmium (Cd2+).