Low CD38 Identifies Progenitor-like Inflammation-Associated Luminal Cells that Can Initiate Human Prostate Cancer and Predict Poor Outcome

Inflammation is a risk factor for prostate cancer, but the mechanisms by which inflammation increases that risk are poorly understood. Here, we demonstrate that low expression of CD38 identifies a progenitor-like subset of luminal cells in the human prostate. CD38lo luminal cells are enriched in glands adjacent to inflammatory cells and exhibit epithelial nuclear factor κB (NF-κB) signaling. In response to oncogenic transformation, CD38lo luminal cells can initiate human prostate cancer in an in vivo tissue-regeneration assay. Finally, the CD38lo luminal phenotype and gene signature are associated with disease progression and poor outcome in prostate cancer. Our results suggest that prostate inflammation expands the pool of progenitor-like target cells susceptible to tumorigenesis. [Display omitted] •Low expression of CD38 enriches for luminal progenitor cells in human prostate•CD38lo luminal cells are localized in proximity to prostatic inflammation•CD38lo luminal cells are target cells for aggressive human prostate cancer•Low CD38 in prostate cancer is prognostic for biochemical recurrence and metastasis Chronic inflammation of the prostate is a risk factor for cancer, but how inflammation increases disease risk remains poorly defined. Liu et al. show that luminal progenitor cells expressing low levels of CD38 are expanded around inflammation, and these progenitors are target cells that can initiate human prostate cancer.