How urinary bladder tumors grow and expand: The bladder as a model for the study of clonal organization and field cancerization

膀胱癌是研究肿瘤发生和发展的最佳模型之一：1)遗传和环境因素共同作用，2)两种主要疾病表型(非侵袭性乳头状癌和侵袭性膀胱癌)已被公认，3)进展发生在不同的遗传途径，4)多个同步或异时性肿瘤经常被发现，5)在非肿瘤性尿路上皮中场效应已被报道。此外，膀胱癌具有社会相关性，因为它为卫生系统产生了每名患者最高的成本。在这个项目中，将通过关注上皮干细胞的概念来检查肿瘤的发展和扩散的步骤。我们希望确定尿路上皮干细胞的位置，并追踪克隆后代及其在不同膀胱癌表型中的变化。这将通过组织化学方法来检测细胞色素c氧化酶的活性，以及线粒体和核DNA测序。这种组织形态学方法将首次允许二维深入了解膀胱肿瘤的生长和发展，并将帮助病理学家和临床医生更好地了解这种多种多样的疾病。

Bladder cancer is one of the best models to study tumour development and pro-gression: 1) both genetic and environmental factors contribute as causes, 2) two major disease phenotypes (non-invasive papillary and invasive) have been recognized, 3) progression occurs following distinct genetic pathways, 4) multiple syn- or metachronous tumours are often found, and 5) a “field effect” has been reported in the non-neoplastic urothelium. In addition, bladder cancer is socially relevant, as it generates the highest costs/patient to the health system. In this project, the steps of tumour development and spread will be examined by focusing on the epithelial stem cell concept. We want to identify the urothelial stem cell location and trace the clonal progeny as well as its changes in different bladder cancer pheno-types. This will be carried out by a histochemical method to detect activity of cytochrome c oxidase, and mitochondrial and nuclear DNA-sequencing. This histo-morphological approach will allow for the first time two-dimensional insights into the growth and the development of bladder tumours and will help pathologists and clinicians to understand better such a versatile disease.