Abstract 3446: Fibroblast growth factor 23 promotes prostate cancer cell proliferation and invasiveness in vitro

Abstract

Abstract Prostate cancer is the most common malignancy among American men and remains the second leading cause of male cancer mortality. Since age is thought to be one of the crucial factors in prostate cancer development, fibroblast growth factor 23 (FGF23), which forms a complex with Klotho, the age-related gene product, could play a key role in prostate development and progression. FGF23 is a peptide hormone member of the endocrine FGF subfamily (FGF19, FGF21, and FGF23), which signals through FGF receptors (FGFRs) in the presence of the coreceptor α-Klotho. FGF-23 has a critical role in phosphate homeostasis and vitamin D metabolism. The regulation of 1,25-Dihydroxyvitamin D by FGF-23 could also have implications for cancers, given that vitamin D metabolites have been shown to have anticarcinogenic effects. It has been reported that higher concentrations of FGF-23 were found in patients with advanced ovarian cancer compared with those with early-stage cancer or control subjects; circulating FGF-23 is associated with an increased risk of colorectal adenoma; however, to date, no investigations of the role of FGF-23 in prostate cancer have been reported. In the present study we investigated the function of FGF23 on human prostate cancer progression. FGF23 gene expression was determined in the commonly used prostate cancer cell lines: PC3, LNCaP, DU145, VCaP, and an immortalized normal prostate cell line PNTIA. RT-PCR showed that both FGF23 and αKlotho (KLA) genes are expressed in all these cell lines. Quantitative real-time RT-PCR indicated that FGF23 gene expression is elevated in prostate cancer compared to normal prostate tissue; FGF23 expression frequency is significantly higher in prostate cancer in compare with normal tissue (prostate cancer: total case number 35, positive 23; normal prostate tissue: total number 33, positive 15; p=0.04841). Biological function assays demonstrated that exogenous FGF23 stimulates prostate cancer cell proliferation (LNCaP by 30%, PC3 20%), anchorage-independent growth (by 60% for both LNCaP and PC3 cells), and invasion (LNCaP by 50% and PC3 55%). Suppression of FGF23 expression by FGF23 short hairpin RNA (shRNA) significantly inhibits PC3 and LNCaP cell proliferation, soft agar colony formation, and invasiveness in vitro. These data suggest that FGF23 promotes human prostate cancer progression and targeting FGF23 signaling pathway could decrease prostate cancer growth and metastasis. Citation Format: Shu Feng, Michael Ittmann. Fibroblast growth factor 23 promotes prostate cancer cell proliferation and invasiveness in vitro. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3446. doi:10.1158/1538-7445.AM2014-3446