Abstract 3283: The role of formyl peptide receptor 1 (FPR1) in neuroblastoma tumorigenesis

Abstract

Abstract The formyl peptide receptor 1 (FPR1) is a G protein-coupled receptor with pattern recognition properties and is mainly expressed by myeloid cells. It is involved in a broad range of host defense mechanisms and a variety of host-derived agonists of FPR1 have been identified, including formyl peptides released from disrupted mitochondria of necrotic cells. In the present study, we demonstrate the expression of FPR1 in 7 different neuroblastoma cell lines and in primary tumors. Furthermore, FPR1 is expressed at increased levels in high stage tumors. Addition of the FPR1 agonist N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP) to neuroblastoma cells in vitro caused enhanced proliferative activity, increase of intracellular calcium response and activation of STAT3 and MAPK/ERK signal transduction pathways. All these signal transduction events were abrogated by the use of Cyclosporin H, a specific FPR1 antagonist. To assess the significance of this receptor in vivo, we developed a set of neuroblastoma cell clones with different expression levels of FPR1. Xenograft models showed that cells with overexpression of the receptor developed tumors significantly faster compared to control group. Our findings so far suggest that FPR1 may play a significant role in neuroblastoma tumorigenesis and that therapeutic intervention of the FPR1 pathway may be an important clinical strategy in neuroblastoma therapy. Citation Format: Igor Snapkov, Carl Otto Öqvist, Yngve Anton Figenschau, Per Kogner, John Inge Johnsen, Baldur Sveinbjørnsson. The role of formyl peptide receptor 1 (FPR1) in neuroblastoma tumorigenesis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3283. doi:10.1158/1538-7445.AM2015-3283