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GPR56 Plays varying roles in endogenous cancer progression

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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

References

  1. Morgan MR, Humphries MJ, Bass MD (2007) Synergistic control of cell adhesion by integrins and syndecans. Nat Rev Mol Cell Biol 8(12):957–969

    Article  CAS  PubMed  Google Scholar 

  2. Hynes RO (2002) Integrins: bidirectional, allosteric signaling machines. Cell 110(6):673–687

    Article  CAS  PubMed  Google Scholar 

  3. Miranti CK, Brugge JS (2002) Sensing the environment: a historical perspective on integrin signal transduction. Nat Cell Biol 4(4):E83–E90

    Article  CAS  PubMed  Google Scholar 

  4. Streuli CH, Akhtar N (2009) Signal co-operation between integrins and other receptor systems. Biochem J 418(3):491–506

    Article  CAS  PubMed  Google Scholar 

  5. Lagerstrom MC, Schioth HB (2008) Structural diversity of G protein-coupled receptors and significance for drug discovery. Nat Rev Drug Discov 7(4):339–357

    Article  PubMed  Google Scholar 

  6. Stacey M, Chang GW, Davies JQ et al (2003) The epidermal growth factor-like domains of the human EMR2 receptor mediate cell attachment through chondroitin sulfate glycosaminoglycans. Blood 102(8):2916–2924

    Article  CAS  PubMed  Google Scholar 

  7. Kwakkenbos MJ, Pouwels W, Matmati M et al (2005) Expression of the largest CD97 and EMR2 isoforms on leukocytes facilitates a specific interaction with chondroitin sulfate on B cells. J Leukoc Biol 77(1):112–119

    CAS  PubMed  Google Scholar 

  8. Xu L, Begum S, Hearn JD et al (2006) GPR56, an atypical G protein-coupled receptor, binds tissue transglutaminase, TG2, and inhibits melanoma tumor growth and metastasis. Proc Natl Acad Sci USA 103(24):9023–9028

    Article  CAS  PubMed  Google Scholar 

  9. Wang T, Ward Y, Tian L et al (2005) CD97, an adhesion receptor on inflammatory cells, stimulates angiogenesis through binding integrin counterreceptors on endothelial cells. Blood 105(7):2836–2844

    Article  CAS  PubMed  Google Scholar 

  10. Vallon M, Essler M (2006) Proteolytically processed soluble tumor endothelial marker (TEM) 5 mediates endothelial cell survival during angiogenesis by linking integrin alpha(v)beta3 to glycosaminoglycans. J Biol Chem 281(45):34179–34188

    Article  CAS  PubMed  Google Scholar 

  11. Lorand L, Graham RM (2003) Transglutaminases: crosslinking enzymes with pleiotropic functions. Nat Rev Mol Cell Biol 4(2):140–156

    Article  CAS  PubMed  Google Scholar 

  12. Xu L, Hynes RO (2007) GPR56 and TG2: possible roles in suppression of tumor growth by the microenvironment. Cell Cycle 6(2):160–165

    CAS  PubMed  Google Scholar 

  13. Li S, Jin Z, Koirala S et al (2008) GPR56 regulates pial basement membrane integrity and cortical lamination. J Neurosci 28(22):5817–5826

    Article  CAS  PubMed  Google Scholar 

  14. Koirala S, Jin Z, Piao X et al (2009) GPR56-regulated granule cell adhesion is essential for rostral cerebellar development. J Neurosci 29(23):7439–7449

    Article  CAS  PubMed  Google Scholar 

  15. Zendman AJ, Cornelissen IM, Weidle UH et al (1999) TM7XN1, a novel human EGF-TM7-like cDNA, detected with mRNA differential display using human melanoma cell lines with different metastatic potential. FEBS Lett 446(2–3):292–298

    Article  CAS  PubMed  Google Scholar 

  16. Shashidhar S, Lorente G, Nagavarapu U et al (2005) GPR56 is a GPCR that is overexpressed in gliomas and functions in tumor cell adhesion. Oncogene 24(10):1673–1682

    Article  CAS  PubMed  Google Scholar 

  17. Sud N, Sharma R, Ray R et al (2006) Differential expression of G-protein coupled receptor 56 in human esophageal squamous cell carcinoma. Cancer Lett 233(2):265–270

    Article  CAS  PubMed  Google Scholar 

  18. Frese KK, Tuveson DA (2007) Maximizing mouse cancer models. Nat Rev Cancer 7(9):645–658

    Article  CAS  PubMed  Google Scholar 

  19. Greenberg NM, DeMayo F, Finegold MJ et al (1995) Prostate cancer in a transgenic mouse. Proc Natl Acad Sci USA 92(8):3439–3443

    Article  CAS  PubMed  Google Scholar 

  20. Lin EY, Jones JG, Li P et al (2003) Progression to malignancy in the polyoma middle T oncoprotein mouse breast cancer model provides a reliable model for human diseases. Am J Pathol 163(5):2113–2126

    PubMed  Google Scholar 

  21. Chin L, Pomerantz J, Polsky D et al (1997) Cooperative effects of INK4a and ras in melanoma susceptibility in vivo. Genes Dev 11(21):2822–2834

    Article  CAS  PubMed  Google Scholar 

  22. Kaplan-Lefko PJ, Chen TM, Ittmann MM et al (2003) Pathobiology of autochthonous prostate cancer in a pre-clinical transgenic mouse model. Prostate 55(3):219–237

    Article  PubMed  Google Scholar 

  23. Wong SY, Haack H, Kissil JL et al (2007) Protein 4.1B suppresses prostate cancer progression and metastasis. Proc Natl Acad Sci USA 104(31):12784–12789

    Article  CAS  PubMed  Google Scholar 

  24. Gingrich JR, Barrios RJ, Morton RA et al (1996) Metastatic prostate cancer in a transgenic mouse. Cancer Res 56(18):4096–4102

    CAS  PubMed  Google Scholar 

  25. Hurwitz AA, Foster BA, Allison JP, et al (2001) The TRAMP mouse as a model for prostate cancer. Curr Protoc Immunol, Chap. 20: Unit 20 5

  26. Sharpless E, Chin L (2003) The INK4a/ARF locus and melanoma. Oncogene 22(20):3092–3098

    Article  CAS  PubMed  Google Scholar 

  27. Galle J, Aust G, Schaller G et al (2006) Individual cell-based models of the spatial-temporal organization of multicellular systems–achievements and limitations. Cytometry A 69(7):704–710

    CAS  PubMed  Google Scholar 

  28. Nishimori H, Shiratsuchi T, Urano T et al (1997) A novel brain-specific p53-target gene, BAI1, containing thrombospondin type 1 repeats inhibits experimental angiogenesis. Oncogene 15(18):2145–2150

    Article  CAS  PubMed  Google Scholar 

  29. Terskikh AV, Easterday MC, Li L et al (2001) From hematopoiesis to neuropoiesis: evidence of overlapping genetic programs. Proc Natl Acad Sci USA 98(14):7934–7939

    Article  CAS  PubMed  Google Scholar 

  30. Terskikh AV, Miyamoto T, Chang C et al (2003) Gene expression analysis of purified hematopoietic stem cells and committed progenitors. Blood 102(1):94–101

    Article  CAS  PubMed  Google Scholar 

  31. Akimov SS, Krylov D, Fleischman LF et al (2000) Tissue transglutaminase is an integrin-binding adhesion coreceptor for fibronectin. J Cell Biol 148(4):825–838

    Article  CAS  PubMed  Google Scholar 

  32. Akimov SS, Belkin AM (2001) Cell surface tissue transglutaminase is involved in adhesion and migration of monocytic cells on fibronectin. Blood 98(5):1567–1576

    Article  CAS  PubMed  Google Scholar 

  33. Iguchi T, Sakata K, Yoshizaki K et al (2008) Orphan G protein-coupled receptor GPR56 regulates neural progenitor cell migration via a G alpha 12/13 and Rho pathway. J Biol Chem 283(21):14469–14478

    Article  CAS  PubMed  Google Scholar 

  34. Hall A (2009) The cytoskeleton and cancer. Cancer Metastasis Rev 28(1–2):5–14

    Article  PubMed  Google Scholar 

Download references

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

Authors and 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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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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