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

  • A. Palangi
  • N. Shakhssalim
  • M. Parvin
  • S. Bayat
  • A. AllamehEmail author
Research Article
  • 30 Downloads

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.

Keywords

Sphingosine 1 phosphate S1P S1P receptor Bladder cancer Urothelial tumor Tumor grade 

Notes

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.

Compliance with ethical standards

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.

References

  1. 1.
    Mitra AP, Cote RJ. Molecular pathogenesis and diagnostics of bladder cancer. Annu Rev Pathol Mech Dis. 2009;28(4):251–85.CrossRefGoogle Scholar
  2. 2.
    Pyne NJ, Pyne S. Sphingosine 1-phosphate and cancer. Nat Rev Cancer. 2010;10(7):489.CrossRefGoogle Scholar
  3. 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.CrossRefGoogle Scholar
  4. 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.CrossRefGoogle Scholar
  5. 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.CrossRefGoogle Scholar
  6. 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.CrossRefGoogle Scholar
  7. 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.CrossRefGoogle Scholar
  8. 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.CrossRefGoogle Scholar
  9. 9.
    Leong WI, Saba JD. S1P metabolism in cancer and other pathological conditions. Biochimie. 2010;92(6):716–23.CrossRefGoogle Scholar
  10. 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.CrossRefGoogle Scholar
  11. 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.CrossRefGoogle Scholar
  12. 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.Google Scholar
  13. 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.CrossRefGoogle Scholar
  14. 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.CrossRefGoogle Scholar
  15. 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.CrossRefGoogle Scholar
  16. 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.CrossRefGoogle Scholar
  17. 17.
    Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative C T method. Nat Protoc. 2008;3(6):1101.CrossRefGoogle Scholar
  18. 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.CrossRefGoogle Scholar
  19. 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.CrossRefGoogle Scholar
  20. 20.
    Frantzi M, Makridakis M, Vlahou A. Biomarkers for bladder cancer aggressiveness. Curr Opin Urol. 2012;22(5):390–6.CrossRefGoogle Scholar
  21. 21.
    Rosen H, Goetzl EJ. Sphingosine 1-phosphate and its receptors: an autocrine and paracrine network. Nat Rev Immunol. 2005;5(7):560.CrossRefGoogle Scholar
  22. 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.CrossRefGoogle Scholar
  23. 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.CrossRefGoogle Scholar
  24. 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.CrossRefGoogle Scholar
  25. 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.Google Scholar
  26. 26.
    Fernandez-Marcos PJ, Serrano M, Maraver A. Bladder cancer and the Notch pathway. Oncotarget. 2015;6(3):1346.CrossRefGoogle Scholar
  27. 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.CrossRefGoogle Scholar

Copyright information

© Federación de Sociedades Españolas de Oncología (FESEO) 2019

Authors and Affiliations

  1. 1.Department of Clinical Biochemistry, Faculty of Medical SciencesTarbiat Modares UniversityTehranIran
  2. 2.Urology and Nephrology Research Center, Shahid Labbafinejad Medical CenterShahid Beheshti University of Medical SciencesTehranIran
  3. 3.Department of Pathology, Shahid Labbafinejad HospitalShahid Beheshti University of Medical SciencesTehranIran
  4. 4.Department of Biochemistry, Faculty of SciencePayam Noor University Tehran UnitTehranIran

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