Skip to main content

Advertisement

SpringerLink
Log in

Differential expression of S1P receptor subtypes in human bladder transitional cell carcinoma

  • Research Article
  • Published:
Clinical and Translational Oncology Aims and scope Submit manuscript

Abstract

Purpose

Sphingosine 1 phosphate (S1P), S1P receptors (S1PRs) and their signaling pathways play an important role in the fate of cancer cells. The expression pattern of S1PR subtypes (S1PR1–S1PR5) may alter in cancer development stages, depending on the origin and the pathologic features of tumors. The present study aimed to examine the relationship between plasma S1P levels and the expression of S1PR subtypes in bladder tumors.

Methods/patients

These changes were evaluated in terms of the pathologic grades and stages of human bladder cancer samples. For this, tumor biopsies from 41 new bladder cancer patients as well as 26 normal-looking bladder tissues were collected and processed for immunohistochemistry (IHC) and quantitative real-time RT-PCR of S1PR subtypes. Plasma S1P level was measured using liquid chromatography–tandem mass spectrometry (LC–MS/MS).

Results

The results show that tissue S1PR1, S1PR2 and S1PR3 are over-expressed in all tumors regardless of their pathological grade (~ 3, ~ 6 and ~ 104 folds, respectively). These results were corroborated by IHC data showing accumulation of S1PR subtypes 1 and 2 in the tissues. Plasma S1P in the plasma samples from patients was in the range of control samples (Controls; 256 ± 47; patients, 270 ± 41).

Conclusions

Overexpression of S1PR1, S1PR2 and S1PR3 in bladder tumor biopsies which were corroborated with the pathological grades and stages may suggest that S1PR profile in tumor biopsies is a promising marker in the diagnosis of bladder carcinoma.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Mitra AP, Cote RJ. Molecular pathogenesis and diagnostics of bladder cancer. Annu Rev Pathol Mech Dis. 2009;28(4):251–85.

    Article  CAS  Google Scholar 

  2. Pyne NJ, Pyne S. Sphingosine 1-phosphate and cancer. Nat Rev Cancer. 2010;10(7):489.

    Article  CAS  PubMed  Google Scholar 

  3. Vadas M, Xia P, McCaughan G, Gamble J. The role of sphingosine kinase 1 in cancer: oncogene or non-oncogene addiction? Biochim Biophys Acta. 2008;1781(9):442–7.

    Article  CAS  PubMed  Google Scholar 

  4. Takabe K, Kim RH, Allegood JC, Mitra P, Ramachandran S, Nagahashi M, et al. Estradiol induces export of sphingosine-1-phosphate from breast cancer cells via ABCC1 and ABCG2. J Biol Chem. 2010;285:10477–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Liang J, Nagahashi M, Kim EY, Harikumar KB, Yamada A, Huang WC, et al. Sphingosine-1-phosphate links persistent STAT3 activation, chronic intestinal inflammation, and development of colitis-associated cancer. Cancer Cell. 2013;23(1):107–20.

    Article  CAS  PubMed  Google Scholar 

  6. Nunes J, Naymark M, Sauer L, Muhammad A, Keun H, Sturge J, et al. Circulating sphingosine-1-phosphate and erythrocyte sphingosine kinase-1 activity as novel biomarkers for early prostate cancer detection. Br J Cancer. 2012;106(5):909.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Gao XY, Li L, Wang XH, Wen XZ, Ji K, Ye L, et al. Inhibition of sphingosine-1-phosphate phosphatase 1 promotes cancer cells migration in gastric cancer: clinical implications Corrigendum. Oncol Rep. 2015;34(4):1977–87. https://doi.org/10.3892/or.2018.6269.

    Article  CAS  PubMed  Google Scholar 

  8. Zhao J, Liu J, Lee JF, Zhang W, Kandouz M, Van Hecke GC, et al. TGF-β/SMAD3 pathway stimulates sphingosine-1-phosphate receptor 3 expression: implication of sphingosine-1-phosphate receptor 3 in lung adenocarcinoma progression. J Biol Chem. 2016;291:27343–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Leong WI, Saba JD. S1P metabolism in cancer and other pathological conditions. Biochimie. 2010;92(6):716–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Maceyka M, Harikumar KB, Milstien S, Spiegel S. Sphingosine-1-phosphate signaling and its role in disease. Trends Cell Biol. 2012;22(1):50–60.

    Article  CAS  PubMed  Google Scholar 

  11. Yamaguchi H, Kitayama J, Takuwa N, Arikawa K, Inoki I, Takehara K, et al. Sphingosine-1-phosphate receptor subtype-specific positive and negative regulation of Rac and haematogenous metastasis of melanoma cells. Biochem J. 2003;374(3):715–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Goetzl EJ, Dolezalova H, Kong Y, Zeng L. Dual mechanisms for lysophospholipid induction of proliferation of human breast carcinoma cells. Can Res. 1999;59(18):4732–7.

    CAS  Google Scholar 

  13. Van Brocklyn JR, Young N, Roof R. Sphingosine-1-phosphate stimulates motility and invasiveness of human glioblastoma multiforme cells. Cancer Lett. 2003;199(1):53–60.

    Article  CAS  PubMed  Google Scholar 

  14. Yamashita H, Kitayama J, Shida D, Yamaguchi H, Mori K, Osada M, et al. Sphingosine 1-phosphate receptor expression profile in human gastric cancer cells: differential regulation on the migration and proliferation1. J Surg Res. 2006;130(1):80–7.

    Article  CAS  PubMed  Google Scholar 

  15. Babjuk M, Burger M, Zigeuner R, Shariat SF, van Rhijn BW, Compérat E, et al. EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder: update 2013. Eur Urol. 2013;64(4):639–53.

    Article  Google Scholar 

  16. Taylor S, Wakem M, Dijkman G, Alsarraj M, Nguyen M. A practical approach to RT-qPCR—publishing data that conform to the MIQE guidelines. Methods. 2010;50(4):S1–5.

    Article  CAS  PubMed  Google Scholar 

  17. Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative C T method. Nat Protoc. 2008;3(6):1101.

    Article  CAS  Google Scholar 

  18. Schmidt H, Schmidt R, Geisslinger G. LC–MS/MS-analysis of sphingosine-1-phosphate and related compounds in plasma samples. Prostaglandins Other Lipid Mediat. 2006;81(3–4):162–70.

    Article  CAS  PubMed  Google Scholar 

  19. Compérat E, Varinot J, Moroch J, Eymerit-Morin C, Brimo F. A practical guide to bladder cancer pathology. Nat Rev Urol. 2018;15(3):143.

    Article  PubMed  Google Scholar 

  20. Frantzi M, Makridakis M, Vlahou A. Biomarkers for bladder cancer aggressiveness. Curr Opin Urol. 2012;22(5):390–6.

    Article  PubMed  Google Scholar 

  21. Rosen H, Goetzl EJ. Sphingosine 1-phosphate and its receptors: an autocrine and paracrine network. Nat Rev Immunol. 2005;5(7):560.

    Article  CAS  PubMed  Google Scholar 

  22. Go H, Kim PJ, Jeon YK, Cho YM, Kim K, Park BH, et al. Sphingosine-1-phosphate receptor 1 (S1PR1) expression in non-muscle invasive urothelial carcinoma: association with poor clinical outcome and potential therapeutic target. Eur J Cancer. 2015;51(14):1937–45.

    Article  CAS  PubMed  Google Scholar 

  23. Patmanathan SN, Wang W, Yap LF, Herr DR, Paterson IC. Mechanisms of sphingosine 1-phosphate receptor signalling in cancer. Cell Signal. 2017;1(34):66–75.

    Article  CAS  Google Scholar 

  24. Williams PA, Stilhano RS, To VP, Tran L, Wong K, Silva EA. Hypoxia augments outgrowth endothelial cell (OEC) sprouting and directed migration in response to sphingosine-1-phosphate (S1P). PLoS One. 2015;10(4):e0123437.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Vaupel P, Kallinowski F, Okunieff P. Blood flow, oxygen and nutrient supply, and metabolic microenvironment of human tumors: a review. Can Res. 1989;49(23):6449–65.

    CAS  Google Scholar 

  26. Fernandez-Marcos PJ, Serrano M, Maraver A. Bladder cancer and the Notch pathway. Oncotarget. 2015;6(3):1346.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Pignot G, Cizeron-Clairac G, Vacher S, Susini A, Tozlu S, Vieillefond A, et al. microRNA expression profile in a large series of bladder tumors: identification of a 3-miRNA signature associated with aggressiveness of muscle-invasive bladder cancer. Int J Cancer. 2013;132(11):2479–91.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This research is part of the PhD thesis of Alireza Palangi, Department of Clinical Biochemistry, Faculty of Medical Science, Tarbiat Modares University, Tehran, Iran and has been partially financially supported by project number 5892 from the Urology and Nephrology Research Center, Shahid Labbafinejad Medical center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Author information

Authors and Affiliations

  1. Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran

    A. Palangi & A. Allameh

  2. Urology and Nephrology Research Center, Shahid Labbafinejad Medical Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    N. Shakhssalim

  3. Department of Pathology, Shahid Labbafinejad Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    M. Parvin

  4. Department of Biochemistry, Faculty of Science, Payam Noor University Tehran Unit, Tehran, Iran

    S. Bayat

Authors
  1. A. Palangi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. N. Shakhssalim
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. Parvin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S. Bayat
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A. Allameh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A. Allameh.

Ethics declarations

Conflict of interest

The authors declare that there are no conflicts of interest concerning this study.

Ethical approval

This study has been approved by the ethical committee of Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Informed consent

Informed consent was obtained from all participants included in this study.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Palangi, A., Shakhssalim, N., Parvin, M. et al. Differential expression of S1P receptor subtypes in human bladder transitional cell carcinoma. Clin Transl Oncol 21, 1240–1249 (2019). https://doi.org/10.1007/s12094-019-02049-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12094-019-02049-3

Keywords

Search

Navigation