Olfactomedin 4 Suppresses Prostate Cancer Cell Growth and Metastasis via Negativ

Olfactomedin 4 （OLFM4）在正常前列腺上皮细胞中表达，并在正常人前列腺上皮细胞（RWPE1）中永生化，但在这些群体中表达OLFM4的细胞的身份以及OLFM4在这些细胞中的生理功能尚不清楚。我们之前也报道了人类嗅素4 （OLFM4）基因在正常成人前列腺中表现出干细胞/祖细胞特性的俱乐部细胞和丘细胞中表达，并且OLFM4功能介导人类前列腺干细胞/祖细胞的增殖和分化。然而，Olfm4+细胞在小鼠前列腺中的分布和功能尚不完全清楚。在本研究中，我们在成年小鼠前列腺前腔上皮和尿道管中发现了Olfm4+细胞。利用Olfm4eGFP报告小鼠系，我们观察到Olfm4在出生后早期发育过程中在泌尿生殖和前列腺上皮细胞中表达，并在尿道管和前列腺前上皮中持续表达至成年。通过体外前列腺球和前列腺静态类器官形成实验，我们证明了Olfm4+成年Olfm4eGFP小鼠前列腺细胞是双能干细胞/祖细胞和单能腔祖细胞。Olfm4eGFP小鼠是进一步研究Olfm4s生物学功能的新模型，可以为Olfm4s在人类发育和疾病中的作用提供新的见解。

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.