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GPR56 Plays varying roles in endogenous cancer progression

Clinical & Experimental Metastasis volume 27, pages 241–249 (2010)Cite this article

Abstract

GPR56, a non-classical adhesion receptor, was previously reported to suppress tumor growth and metastasis in xenograft models using human melanoma cell lines. To understand whether GPR56 plays similar roles in the development of endogenous tumors, we analyzed cancer progression in Gpr56 −/− mice using a variety of transgenic cancer models. Our results showed that GPR56 suppressed prostate cancer progression in the TRAMP model on a mixed genetic background, similar to its roles in progression of melanoma xenografts. However, its roles in other cancer types appeared to be complex. It had marginal effects on tumor onset of mammary tumors in the MMTV–PyMT model, but had no effects on subsequent tumor progression in either the MMTV–PyMT mice or the melanoma model, Ink4a/Arf −/− tyr-Hras. These results indicate diverse roles of GPR56 in cancer progression and provide the first genetic evidence for the involvement of an adhesion GPCR in endogenous cancer development.

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Abbreviations

BFPP:

Bilateral frontoparietal polymicrogyria

ECM:

Extracellular matrix

GPCR:

G protein-coupled receptor

GPR56:

G protein-coupled receptor 56

MMTV:

Mouse mammary tumor virus

PyMT:

Polyoma middle T oncogene

RIPA:

Radio-immunoprecipitation assay

TG2:

Tissue transglutaminase

TRAMP:

Transgenic adenocarcinoma of the mouse prostate

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Acknowledgments

We thank Dr. Rulang Jiang and Dr. Sunny Wong for critical reading of the manuscript. We also thank Dr. Sunny Wong for sharing protein lysates from the prostate cancer cell lines. This work was supported by grants from the NIH (U54CA126515, R.O.H), the Virginia and Daniel K Ludwig Fund for Cancer Research (R.O.H), and the Howard Hughes Medical Institute (R.O.H).

Author information

Author notes

  1. Lei Xu

    Present address: Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, NY, 14642, USA

  2. Marc Barry

    Present address: Department of Pathology, MSC084640, 1 University of New Mexico, Albuquerque, NM, 87131-0001, USA

Affiliations

  1. Howard Hughes Medical Institute and Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA

    Lei Xu, Shahinoor Begum, Marc Barry, Denise Crowley & Richard O. Hynes

  2. Department of Biomedical Sciences, Tufts University School of Veterinary Medicine, North Grafton, MA, 01536, USA

    Roderick T. Bronson

  3. Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, NY, 14642, USA

    Liquan Yang

Authors
  1. Lei Xu
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  2. Shahinoor Begum
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  3. Marc Barry
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  4. Denise Crowley
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  5. Liquan Yang
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  6. Roderick T. Bronson
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  7. Richard O. Hynes
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Corresponding author

Correspondence to Lei Xu.

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Xu, L., Begum, S., Barry, M. et al. GPR56 Plays varying roles in endogenous cancer progression. Clin Exp Metastasis 27, 241–249 (2010). https://doi.org/10.1007/s10585-010-9322-3

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Keywords

  • GPR56
  • Prostate cancer
  • Breast cancer
  • Melanoma
  • Animal models on cancer