Lineage analysis of basal epithelial cells reveals their unexpected plasticity and supports a cell-of-origin model for prostate cancer heterogeneity

Zhu A. Wang, Antonina Mitrofanova, Sarah K. Bergren, Cory Abate-Shen, Robert D. Cardiff, Andrea Califano, Michael M. Shen

Research output: Contribution to journalArticle

173 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)274-283
Number of pages10
JournalNature cell biology
Volume15
Issue number3
DOIs
StatePublished - Mar 2013

All Science Journal Classification (ASJC) codes

  • Cell Biology

Fingerprint Dive into the research topics of 'Lineage analysis of basal epithelial cells reveals their unexpected plasticity and supports a cell-of-origin model for prostate cancer heterogeneity'. Together they form a unique fingerprint.

  • Cite this