Hepatoma-derived growth factor: A survival-related protein in prostate oncogenesis and a potential target for vitamin K2

• Published in: Urologic oncology Vol. 34; no. 11; pp. 483.e1 - 483.e8
• Main Authors: Shetty, Aditya, M.D, Dasari, Subramanyam, Ph.D, Banerjee, Souresh, M.S, Gheewala, Taher, M.S, Zheng, Guoxing, Ph.D, Chen, Aoshuang, Ph.D, Kajdacsy-Balla, Andre, M.D., Ph.D, Bosland, Maarten C., DVSc, Ph.D, Munirathinam, Gnanasekar, Ph.D
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2016
• Subjects: Adenocarcinoma - metabolism; Adenocarcinoma - pathology; AKT; Androgens; Antibodies, Monoclonal - pharmacology; Apoptosis - drug effects; Cell Division - drug effects; Cell Line, Tumor; Cell Survival; Cell Transformation, Neoplastic; Drug Screening Assays, Antitumor; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Gene Expression Regulation, Neoplastic; HDGF; Humans; Intercellular Signaling Peptides and Proteins - pharmacology; Intercellular Signaling Peptides and Proteins - physiology; Invasion; Male; Migration; Molecular Targeted Therapy; Neoplasm Proteins - biosynthesis; Neoplasm Proteins - genetics; Neoplasms, Hormone-Dependent - metabolism; Neoplasms, Hormone-Dependent - pathology; NF-kappa B - metabolism; NF-kB; Proliferation; Prostate - cytology; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Prostatic Neoplasms, Castration-Resistant - metabolism; Prostatic Neoplasms, Castration-Resistant - pathology; Recombinant Proteins - metabolism; RNA Interference; RNA, Small Interfering - pharmacology; Urology; Vitamin K 2 - pharmacology; Vitamin K2; Migration; NF-kB; Vitamin K2; HDGF; AKT; Proliferation; Invasion
• ISSN: 1078-1439; 1873-2496
• DOI: 10.1016/j.urolonc.2016.05.027

Abstract Hepatoma-derived growth factor (HDGF) is a heparin-binding growth factor, which has previously been shown to be expressed in a variety of cancers. HDGF overexpression has also previously been correlated with a poor prognosis in several cancers. The significance of HDGF in prostate cancer, however, has not been investigated. Here, we show that HDGF is overexpressed in both androgen-sensitive LNCaP cells and androgen-insensitive DU145, 22RV1, and PC-3 cells. Forced overexpression enhanced cell viability of RWPE-1 cells, whereas HDGF knockdown reduced cell proliferation in human prostate cancer cells. We also show that HDGF may serve as a survival-related protein as ectopic overexpression of HDGF in RWPE cells up-regulated the expression of antiapoptosis proteins cyclin E and BCL-2, whereas simultaneously down-regulating proapoptotic protein BAX. Western blot analysis also showed that HDGF overexpression modulated the activity of phospho-AKT as well as NF-kB, and these results correlated with in vitro migration and invasion assays. We next assessed the therapeutic potential of HDGF inhibition with a HDGF monoclonal antibody and vitamin k2 , showing reduced cell proliferation as well as inhibition of NF-kB expression in HDGF overexpressed RWPE cells treated with a HDGF monoclonal antibody and vitamin K2 . Collectively, our results suggest that HDGF is a relevant protein in prostate oncogenesis and may serve as a potential therapeutic target in prostate cancer.