Bladder cancers arise from distinct urothelial sub-populations
Bladder cancers arise from distinct urothelial sub-populations
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DOI：
10.1038/ncb3038
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发表时间：
2014-10-01
影响因子：
21.3
通讯作者：
Mendelsohn, Cathy
中科院分区：
文献类型：
--
作者：
Van Batavia, Jason;Yamany, Tammer;Mendelsohn, Cathy
膀胱癌是人类第六大常见癌症。这种异质性病变包括尿路上皮癌（Uca）和鳞状细胞癌（SCC），起源于尿路上皮，一种由表达K5的基底细胞、中间细胞和伞细胞组成的复层上皮。浅表Uca病变在形态上不同，表现出不同的临床行为：原位癌（CIS）是一种扁平的侵袭性病变，而乳头状癌通常是低级别和非侵袭性的。这些不同的特征是否反映了不同的细胞类型的起源是未知的。在这里，我们使用谱系追踪在小鼠模型中的癌发生，中间细胞主要引起乳头状病变，而K5-基底细胞可能是CIS，肌肉浸润性病变和SCC的祖先取决于遗传背景。我们的研究结果为膀胱癌病变的多样性提供了细胞和遗传基础，并为它们的临床和形态学差异提供了可能的解释。
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.