Journal Article

Bladder cancers arise from distinct urothelial sub-populations

Batourina, Ekaterina, Mansukhani, Mahesh, Oyon, Daniel, Cordon-Cardo, Carlos, Schneider, Kerry, Molotkov, Andrei, Yamany, Tammer, Dan, Hanbin, Wu, Xue-Ru, Mendelsohn, Cathy, Van Batavia, Jason, Dunlop, Mark

2014

Overview

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. Mendelsohn and colleagues use lineage tracing in a mouse model of bladder cancer to show that different progenitor cell populations give rise to distinct types of urothelial and squamous cell carcinomas.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 13/1 / 13/100 / 13/51 / 14/63 / 38/1 / 631/136/334/1874/345 / 631/67 / 631/67/70 / 64/60 / 82/51 / Animals / Bladder cancer / Butylhydroxybutylnitrosamine / Cancer cells / Cancer Research / Carcinogenesis / Carcinoma in Situ - chemically induced / Carcinoma in Situ - genetics / Carcinoma in Situ - metabolism / Carcinoma, Papillary - chemically induced / Carcinoma, Papillary - genetics / Carcinoma, Papillary - metabolism / Carcinoma, Squamous Cell - chemically induced / Carcinoma, Squamous Cell - genetics / Carcinoma, Squamous Cell - metabolism / Carcinoma, Transitional Cell - chemically induced / Carcinoma, Transitional Cell - genetics / Carcinoma, Transitional Cell - metabolism / Cell Biology / Cell Lineage / Development and progression / Developmental Biology / Female / Genetic aspects / Humans / Identification and classification / Keratin / Keratin-5 - genetics / Keratin-5 - metabolism / Lesions / Life Sciences / Luminescent Proteins - genetics / Luminescent Proteins - metabolism / Male / Mice, 129 Strain / Mice, Knockout / Mice, Transgenic / Microscopy, Confocal / Mutation / Neoplastic Stem Cells - metabolism / Neoplastic Stem Cells - pathology / Pathology / Stem Cells / Urinary Bladder Neoplasms - chemically induced / Urinary Bladder Neoplasms - genetics / Urinary Bladder Neoplasms - metabolism / Urology