Abstract 4951: FGFRL1 in prostate cancer progression
Authors: Yu Lan , Erickson Andrew , Toriseva Mervi , Elo Teresa , Tuomela Johanna , Seikkula Heikki , Nurmi Martti , Boström Peter , Mirtti Tuomas , Alanen Kalle , Kallajoki Markku , Nees Matthias , Härkönen Pirkko 
Published: July 2016

Abstract
Prostate cancer (PCa) is a disease with high incidence, however, many PCa patients are over-diagnosed and over-treated. Molecular characterization of PCa provides a valid approach to stratify patients, and thus reduce overtreatment. Fibroblast growth factors and their receptor (FGF/FGFR) signaling pathways are involved in various cellular functions such as proliferation, differentiation, migration, and apoptosis of prostate cancer cells. Dysregulated and constitutively activated FGF/FGFR pathways have been shown to be involved in the initiation and progression of prostate cancer. Fibroblast growth factor receptor like 1 (FGFRL1, FGFR5) is the most recently identified member of the FGFR family. FGFRL1 binds several FGFs but its short intracellular part lacks a tyrosine kinase domain. Therefore, the extracellular domain has been suggested to act as a dominant negative regulator of other FGFRs. However, cellular functions of FGFRL1 remain poorly understood. Aberrant FGFRL1 expression has been reported in ovarian, bladder, colon, and other cancers. In silico data analysis indicated altered FGFRL1 mRNA expression in 17% of PCa cases. To date, there have been no systematic studies of FGFRL1 expression and function in prostate and PCa. We studied FGFRL1 expression and function in PCa cell lines, xenografts and in human PCa specimens. FGRL1 was knocked-down in PC-3M cells, by shRNAs, which showed reduced growth as nude mouse xenografts when compared to control. This argues against a dominant negative function. To study FGFRL1 in human PCas, we collected formalin-fixed paraffin-embedded samples from PCa patients undergoing radical prostatectomy (n = 243), metastatic PCa (n = 36) and castration-resistant PCa (n = 21). Samples were prepared for mRNA analysis, and immunohistochemistry. The overall levels of FGFRL1 immunostaining were significantly increased in PCa compared to normal tissue. In normal tissue, FGFRL1 immunostaining localized to the cell membrane and to a lesser extent to the cytoplasm and nuclei. In PCa, protein expression of FGFRL1 was decreased at the cell membrane, while expression in the cytoplasm and nucleus were increased. Low membrane and high nuclear immunostaining of FGFRL1 correlated with high Gleason grade. High nuclear FGFRL1 also correlated with high levels of preoperative serum PSA and an increased proportion of tumors with positive surgical margins. Our results suggest that FGFRL1 may play an active role in PCa cells and in tumor progression and can possibly be used to assess PCa prognosis.
Citation Format: Lan Yu, Andrew Erickson, Mervi Toriseva, Teresa Elo, Johanna Tuomela, Heikki Seikkula, Martti Nurmi, Peter Boström, Tuomas Mirtti, Kalle Alanen, Markku Kallajoki, Matthias Nees, Pirkko Härkönen. FGFRL1 in prostate cancer progression. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4951.