Olfactomedin 4 Suppresses Prostate Cancer Cell Growth and Metastasis via Negativ

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Olfactomedin 4 (OLFM4) is expressed in normal prostate epithelial cells and immortalized in normal human prostate epithelial cells (RWPE1), but the identity of OLFM4-expressing cells within these populations and OLFM4's physiological functions in these cells have not been elucidated. We have also previously reported that the human olfactomedin 4 (OLFM4) gene is expressed in club and hillock cells that exhibit properties of stem/progenitor cells in normal adult prostate and that OLFM4 functionally mediates proliferation and differentiation of human prostate stem/progenitor cells. However, the distribution and function of Olfm4+ cells in murine prostate are not yet fully understood. In this study, we identified Olfm4+ cells in the luminal epithelia of the anterior prostate and urethral tube in adult mice. Using an Olfm4eGFP reporter mouse line, we observed Olfm4 expression in urogenital and prostatic epithelial cells during early postnatal development, which persisted into adulthood in the urethral tube and anterior-prostate epithelium. Using in vitro prostate-sphere and prostatic-organoid formation assays, we demonstrated that Olfm4+ adult Olfm4eGFP mouse prostate cells are bipotent stem/progenitor cells and unipotent luminal progenitors. The Olfm4eGFP mouse is a novel model to study Olfm4s biological functions further and could provide insight into OLFM4s role in human development and disease.