Role of OGR1 in myeloid-derived cells in prostate cancer

Ovarian cancer G-protein-coupled-receptor-1 (OGR1) is a tumor metastasis suppressor in prostate cancer (PCa). OGR1 knockout mice (ogr1 -/-) are grossly normal under physiological conditions, however, reduced melanoma tumorigenesis has been observed, with the mechanisms of this reduction completely unknown. In this work, we demonstrated that OGR1 deficiency in host cells significantly reduced tumorigenesis of PCa in mice. Adoptive transfer of WT CD11b + Gr1 + double positive (DP) cells, but not T cells, was sufficient to allow tumor development in ogr1 -/- mice. The expression of an M1 macrophage marker, inducible nitric oxide synthase (iNOS) was higher and expression of an M2 macrophage marker, arginase-1 (Arg 1) was lower in tumors from ogr1 -/- mice compared with WT mice. Furthermore, coinjection of transgenic adenocarcinoma mouse prostate (TRAMP)-C2 cells with WT, but not ogr1 -/- macrophages, increased tumor incidence in ogr1 -/- mice. T-cell depletion experiments suggested that T cells were required for tumor rejection in ogr1 -/- mice, although OGR1 expression in T cells may not be necessary. In summary, the expression of OGR1 in myeloid-derived cells, especially in DP cells, was required for PCa tumor cell-induced immunosuppression.