Back to Search
Start Over
Cellular origin of bladder neoplasia and tissue dynamics of its progression to invasive carcinoma
- Source :
- Nature Cell Biology. 16:469-478
- Publication Year :
- 2014
- Publisher :
- Springer Science and Business Media LLC, 2014.
-
Abstract
- Understanding how malignancies arise within normal tissues requires identification of the cancer cell of origin and knowledge of the cellular and tissue dynamics of tumour progression. Here we examine bladder cancer in a chemical carcinogenesis model that mimics muscle-invasive human bladder cancer. With no prior bias regarding genetic pathways or cell types, we prospectively mark or ablate cells to show that muscle-invasive bladder carcinomas arise exclusively from Sonic hedgehog (Shh)-expressing stem cells in basal urothelium. These carcinomas arise clonally from a single cell whose progeny aggressively colonize a major portion of the urothelium to generate a lesion with histological features identical to human carcinoma in situ. Shh-expressing basal cells within this precursor lesion become tumour-initiating cells, although Shh expression is lost in subsequent carcinomas. We thus find that invasive carcinoma is initiated from basal urothelial stem cells but that tumour cell phenotype can diverge significantly from that of the cancer cell of origin.
- Subjects :
- Male
Cell type
Time Factors
Genotype
Recombinant Fusion Proteins
Urinary Bladder
Mice, Transgenic
Biology
medicine.disease_cause
Mice
medicine
Carcinoma
Animals
Humans
Cell Lineage
Hedgehog Proteins
Neoplasm Invasiveness
Urothelium
Cell Proliferation
Bladder cancer
Cancer
Cell Biology
medicine.disease
Tumor Burden
Cell biology
Disease Models, Animal
Cell Transformation, Neoplastic
Phenotype
Urinary Bladder Neoplasms
Cancer cell
Immunology
Neoplastic Stem Cells
Cancer research
Butylhydroxybutylnitrosamine
Stem cell
Carcinogenesis
Subjects
Details
- ISSN :
- 14764679 and 14657392
- Volume :
- 16
- Database :
- OpenAIRE
- Journal :
- Nature Cell Biology
- Accession number :
- edsair.doi.dedup.....da74c837893f7a1de1bdd8bb845f893e
- Full Text :
- https://doi.org/10.1038/ncb2956