Luminal Cells Are Favored as the Cell of Origin for Prostate Cancer
Zhu A. Wang,
Roxanne Toivanen,
Sarah K. Bergren,
Pierre Chambon,
Michael M. Shen
Affiliations
Zhu A. Wang
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
Roxanne Toivanen
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
Sarah K. Bergren
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
Pierre Chambon
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS UMR7104, INSERM U964, 67400 Illkirch, France
Michael M. Shen
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
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.
