Luminal Cells Are Favored as the Cell of Origin for Prostate Cancer

• The cell of origin for prostate cancer has been examined in multiple mouse models
• In each case, luminal epithelial cells are favored as the cell of origin in situ
• Isolated basal epithelial cells can give rise to prostate tumors after renal grafting
• Basal cells may often be a cell of mutation that generates luminal cells of origin

SummaryThe 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.

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