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. 2014 Oct;16(10):982-91, 1-5.
doi: 10.1038/ncb3038. Epub 2014 Sep 14.

Bladder cancers arise from distinct urothelial sub-populations

Jason Van Batavia  1 , Tammer Yamany  1 , Andrei Molotkov  1 , Hanbin Dan  1 , Mahesh Mansukhani  2 , Ekaterina Batourina  1 , Kerry Schneider  1 , Daniel Oyon  1 , Mark Dunlop  1 , Xue-Ru Wu  3 , Carlos Cordon-Cardo  4 , Cathy Mendelsohn  1
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Bladder cancers arise from distinct urothelial sub-populations

Jason Van Batavia et al. Nat Cell Biol. 2014 Oct.

Abstract

Bladder cancer is the sixth most common cancer in humans. This heterogeneous set of lesions including urothelial carcinoma (Uca) and squamous cell carcinoma (SCC) arise from the urothelium, a stratified epithelium composed of K5-expressing basal cells, intermediate cells and umbrella cells. Superficial Uca lesions are morphologically distinct and exhibit different clinical behaviours: carcinoma in situ (CIS) is a flat aggressive lesion, whereas papillary carcinomas are generally low-grade and non-invasive. Whether these distinct characteristics reflect different cell types of origin is unknown. Here we show using lineage tracing in a murine model of carcinogenesis that intermediate cells give rise primarily to papillary lesions, whereas K5-basal cells are likely progenitors of CIS, muscle-invasive lesions and SCC depending on the genetic background. Our results provide a cellular and genetic basis for the diversity in bladder cancer lesions and provide a possible explanation for their clinical and morphological differences.

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