Expression and functional analysis of GPR87, an orphan G protein-coupled receptor overexpressed in non small cell lung cancer

B217 G protein-coupled receptors (GPCRs) function as transducer systems, linking extracellular signals from a variety of ligands to intracellular second messenger pathways. While a role for this receptor super-family in the regulation of cell metabolism has been well established, it has more recently been recognized that GPCRs act as important mediators of several pathways relevant to tumorigenesis, including promotion of cell survival, stimulation of proliferation, and induction of angiogenesis. Previously, it has been reported that a purinergic-like receptor, GPR87 (also known as GPR95), is regulated by the tumor suppressor p53 in an in vitro model of testicular germ cell cancer. However, the function and expression profile of this orphan receptor in vivo are, at present, poorly understood.
 We have observed that GPR87 mRNA is overexpressed with high frequency and magnitude in primary human lung tumors. Receptor expression in lung cancer is strictly associated with tumor epithelium, and is not observed in connective tissue, vascular elements, or infiltrating lymphocytes. Overexpression is almost exclusively restricted to adeno- and squamous cell carcinomas of the non-small cell subtype of lung cancers. In contrast, receptor expression is low to undetectable in normal lung and most other tissues examined. GPR87 transfected into HEK293 cells is constitutively active, and co-transfection experiments with chimeric G proteins strongly suggest that the receptor couples to the Gi signaling pathway. These findings may facilitate characterization of the functional role for GPR87 during lung cancer progression.