Format

Send to

Choose Destination
Cell Rep. 2014 Sep 11;8(5):1339-46. doi: 10.1016/j.celrep.2014.08.002. Epub 2014 Aug 28.

Luminal cells are favored as the cell of origin for prostate cancer.

Author information

1
Departments of Medicine, Genetics and Development, Urology, and Systems Biology, Columbia Stem Cell Initiative, Herbert Irving Comprehensive Cancer Center, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
2
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS UMR7104, INSERM U964, 67400 Illkirch, France.
3
Departments of Medicine, Genetics and Development, Urology, and Systems Biology, Columbia Stem Cell Initiative, Herbert Irving Comprehensive Cancer Center, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA. Electronic address: mshen@columbia.edu.

Abstract

The identification of cell types of origin for cancer has important implications for tumor stratification and personalized treatment. For prostate cancer, the cell of origin has been intensively studied, but it has remained unclear whether basal or luminal epithelial cells, or both, represent cells of origin under physiological conditions in vivo. Here, we use a novel lineage-tracing strategy to assess the cell of origin in a diverse range of mouse models, including Nkx3.1(+/-); Pten(+/-), Pten(+/-), Hi-Myc, and TRAMP mice, as well as a hormonal carcinogenesis model. Our results show that luminal cells are consistently the observed cell of origin for each model in situ; however, explanted basal cells from these mice can generate tumors in grafts. Consequently, we propose that luminal cells are favored as cells of origin in many contexts, whereas basal cells only give rise to tumors after differentiation into luminal cells.

PMID:
25176651
PMCID:
PMC4163115
DOI:
10.1016/j.celrep.2014.08.002
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center