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Role of OGR1 in myeloid-derived cells in prostate cancer

Oncogene volume 33, pages 157–164 (2014)Cite this article

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Abstract

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.

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Acknowledgements

We thank Mrs Helen Jan Chin-Sinex from Dr Marc S. Mendonca's lab at Indiana University School of Medicine for technical assistance in the preparation of irradiated TRAMP-C2 tumor cells. We thank Mrs Huiying Gu from Dr Yansheng Du's lab for technical assistance in the preparation of tumor frozen sections. We also thank Dr Caryl Antalis and Dr Cheryl Dsouza for critical reading and editing of the manuscript. This work was supported in part by the National Institutes of Health (RO1 155145 to YX and LZ); and the Mary Fendrich-Hulman Charitable Trust Fund to YX.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Indiana University School of Medicine, Indianapolis, IN, USA

    L Yan, L S Singh & Y Xu

  2. Department of Biotechnology, Manipur University, Canchipur, Manipur, India

    L S Singh

  3. Departments of Lab Medicine & Pathobiology, Immunology, University of Toronto, Toronto General Research Institute University Health Net work, Toronto, Ontario, Canada

    L Zhang

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  1. L Yan
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Correspondence to L Zhang or Y Xu.

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Yan, L., Singh, L., Zhang, L. et al. Role of OGR1 in myeloid-derived cells in prostate cancer. Oncogene 33, 157–164 (2014). https://doi.org/10.1038/onc.2012.566

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