Lineage analysis of basal epithelial cells reveals their unexpected plasticity and supports a cell-of-origin model for prostate cancer heterogeneity
Top Cited Papers
Open Access
- 24 February 2013
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature
- Vol. 15 (3), 274-283
- https://doi.org/10.1038/ncb2697
Abstract
A key issue in cancer biology is whether oncogenic transformation of different cell types of origin within an adult tissue gives rise to distinct tumour subtypes that differ in their prognosis and/or treatment response. We now show that initiation of prostate tumours in basal or luminal epithelial cells in mouse models results in tumours with distinct molecular signatures that are predictive of human patient outcomes. Furthermore, our analysis of untransformed basal cells reveals an unexpected assay dependence of their stem cell properties in sphere formation and transplantation assays versus genetic lineage tracing during prostate regeneration and adult tissue homeostasis. Although oncogenic transformation of basal cells gives rise to tumours with luminal phenotypes, cross-species bioinformatic analyses indicate that tumours of luminal origin are more aggressive than tumours of basal origin, and identify a molecular signature associated with patient outcome. Our results reveal the inherent plasticity of basal cells, and support a model in which different cells of origin generate distinct molecular subtypes of prostate cancer.Keywords
This publication has 54 references indexed in Scilit:
- Adult Murine Prostate Basal and Luminal Cells Are Self-Sustained Lineages that Can Both Serve as Targets for Prostate Cancer InitiationCancer Cell, 2012
- Clonal architecture of human prostatic epithelium in benign and malignant conditionsThe Journal of Pathology, 2011
- The genomic complexity of primary human prostate cancerNature, 2011
- Tracking adult stem cellsEMBO Reports, 2011
- Subtypes of medulloblastoma have distinct developmental originsNature, 2010
- Primitive origins of prostate cancer: In vivo evidence for prostate‐regenerating cells and prostate cancer‐initiating cellsMolecular Oncology, 2010
- Integrative Genomic Profiling of Human Prostate CancerCancer Cell, 2010
- The Ordered Architecture of Murine Ear Epidermis Is Maintained by Progenitor Cells with Random FateDevelopmental Cell, 2010
- A luminal epithelial stem cell that is a cell of origin for prostate cancerNature, 2009
- Distinct types of diffuse large B-cell lymphoma identified by gene expression profilingNature, 2000