Olfactomedin 4 Suppresses Prostate Cancer Cell Growth and Metastasis via Negativ

Olfactomedin 4 通过 Negativ 抑制前列腺癌细胞的生长和转移

• 批准号: 10706165
• 负责人: GRIFFIN RODGERS
• 金额: $ 59.52万
• 依托单位: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10706165
• 关键词: 13q12; 14q; Adult; American; Anterior; Biological; Biological Assay; Biological Process; CXCL12 gene; Cadherins; Cancer Cell Growth; Cancer Etiology; Cathepsins; Cell Adhesion; Cell Proliferation; Cell surface; Cells; Cessation of life; Chromosomes; Colon Carcinoma; Colonic Neoplasms; Diagnosis; Ectopic Expression; Epithelial; Epithelial Cells; Evaluation; Exhibits; Exons; FOXO1A gene; Family; Family member; Genes; Genitourinary system; Goals; Human; Human Development; Human Genome; In Vitro; Inflammation; Lectin; Loss of Heterozygosity; Malignant neoplasm of prostate; Mediating; Messenger RNA; Metastatic Neoplasm to the Bone; Modeling; Molecular; Mus; Natural Immunity; Negativism; Neoplasm Metastasis; OLFM4 gene; Organoids; Physiological; Play; Population; Prognosis; Property; Prostate; Prostatic; Prostatic Epithelium; Prostatic Neoplasms; Proteins; Reporter; Reporting; Retinoblastoma; Role; Seminal fluid; Serum; Solid Neoplasm; Stomach Neoplasms; Susceptibility Gene; Tissues; Tube; Tumor Suppressor Genes; Tumor Suppressor Proteins; Urethra; advanced prostate cancer; cancer type; cell immortalization; forkhead protein; human disease; improved; in vivo; insight; malignant breast neoplasm; malignant stomach neoplasm; men; novel; olfactomedin; postnatal development; progenitor; prostate cancer cell; prostate cancer progression; stem; stem cells

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.

嗅觉介导蛋白4（OLFM 4）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（RWPE 1）中永生化，但这些群体中表达OLFM 4的细胞的身份和OLFM 4在这些细胞中的生理功能尚未阐明。我们以前也报道过，人嗅调节蛋白4（OLFM 4）基因表达的俱乐部和丘细胞，表现出干/祖细胞在正常成人前列腺和OLFM 4功能介导的人前列腺干/祖细胞的增殖和分化。然而，Olfm 4+细胞在小鼠前列腺中的分布和功能尚未完全了解。在这项研究中，我们确定了Olfm 4+细胞的前前列腺和尿道管在成年小鼠的腔上皮。使用Olfm 4 eGFP报告小鼠系，我们观察到Olfm 4表达在泌尿生殖道和前列腺上皮细胞在出生后早期的发展，持续到成年期的尿道管和前列腺前上皮。使用体外前列腺球和前列腺类器官形成测定，我们证明了Olfm 4+成体Olfm 4 eGFP小鼠前列腺细胞是双能干/祖细胞和单能管腔祖细胞。Olfm 4 eGFP小鼠是进一步研究Olfm 4s生物学功能的新模型，可以深入了解OLFM 4s在人类发育和疾病中的作用。