Olfactomedin 4 Suppresses Prostate Cancer Cell Growth and Metastasis via Negativ

National Heart, Lung, And Blood Institute

Investigators

Linked publications, trials & patents

Abstract

Olfactomedin 4 (OLFM4) is associated with the initiation, growth, and clinical outcome of human prostate cancer. However, its biological functions during de novo progression of prostate cancer are still unknown. In this study, we generated an Olfm4–/–/TRAMP murine prostate cancer model to investigate the biological functions of the Olfm4 gene underlying de novo progression of murine prostate cancer. We found that Olfm4–/–/TRAMP mice developed prostate epithelial lesions at 2 months of age and advanced prostate cancer at 5 months of age, and they had a higher frequency of metastasis at 7 to 10 months than Olfm4+/+/TRAMP mice. Histopathological and immunofluorescent staining revealed that tumor tissues obtained from Olfm4–/–/TRAMP mice contained more vimentin-positive stromal tissues in primary well-differentiated tumors, poorly differentiated tumors, and metastatic tumors than did tissues from Olfm4+/+/TRAMP mice. However, we found that castration-resistant tumors were more heterogeneous in their expression of markers of tumor cells and neuroendocrine cells in Olfm4–/–/TRAMP than in Olfm4+/+/TRAMP mice 7-8 months after castration. JQ1, a BET bromodomain inhibitor, significantly inhibited growth of prostatic tumor cell organoids derived from Olfm4–/–/TRAMP mice. Taken together, our results demonstrate that Olfm4 suppresses de novo progression of murine prostate cancer, and the Olfm4–/–/TRAMP murine prostate cancer model we developed can be used for preclinical study of prostate cancer prevention and therapy.