Skip to main content

Advertisement

SpringerLink
Log in

Serum IL-17F combined with VEGF as potential diagnostic biomarkers for oral squamous cell carcinoma

  • Research Article
  • Published:
Tumor Biology

Abstract

Although interleukin (IL) 17A can promote angiogenesis in several tumors, there are limited clinical evidences on cancer about the correlation between serum vascular endothelial growth factor (VEGF) and IL-17F, which is the most homologous to IL-17A. In this study, serum concentration of IL-17F and VEGF from healthy (n = 28), leukoplakia (n = 15), and oral squamous cell carcinoma (OSCC) groups (n = 85) were assessed and showed that IL-17F level was remarkably downregulated from healthy group (394.3 pg/ml) to OSCC group (82.96 pg/ml). Conversely, the OSCC group had a highest level of VEGF (P < 0.05) in whole groups, and there was a negative correlation between IL-17F and VEGF in serum or in the peripheral blood mononuclear cells (PBMCs) at mRNA level. Moreover, the lowest ratio of IL-17F/VEGF was found in OSCC patients (P < 0.05) and lower ratio of IL-17F/VEGF correlated to higher tumor stage and lymph node metastasis. Furthermore, the serum level of IL-17F and the ratio of IL-17F/VEGF were positively associated with the numbers of CD3+ CD4+ T cells, which indicated that serum IL-17F could originate from PBMCs during the development of OSCC, and could be used for the diagnosis by effectively distinguishing OSCC patients from healthy individuals.

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

Similar content being viewed by others

References

  1. Yao Z, Painter SL, Fanslow WC, Ulrich D, Macduff BM, Spriggs MK, et al. Human IL-17: a novel cytokine derived from T cells. J Immunol. 1995;155(12):5483–6.

    CAS  PubMed  Google Scholar 

  2. Kawaguchi M, Onuchic LF, Li XD, Essayan DM, Schroeder J, Xiao HQ, et al. Identification of a novel cytokine, ML-1, and its expression in subjects with asthma. J Immunol. 2001;167(8):4430–5.

    Article  CAS  PubMed  Google Scholar 

  3. Genovese MC, Van den Bosch F, Roberson SA, Bojin S, Biagini IM, Ryan P, et al. LY2439821, a humanized anti-interleukin-17 monoclonal antibody, in the treatment of patients with rheumatoid arthritis: a phase I randomized, double-blind, placebo-controlled, proof-of-concept study. Arthritis Rheum. 2010;62(4):929–39. doi:10.1002/art.27334.

    Article  CAS  PubMed  Google Scholar 

  4. Aujla SJ, Chan YR, Zheng M, Fei M, Askew DJ, Pociask DA, et al. IL-22 mediates mucosal host defense against Gram-negative bacterial pneumonia. Nat Med. 2008;14(3):275–81. doi:10.1038/nm1710.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Doreau A, Belot A, Bastid J, Riche B, Trescol-Biemont MC, Ranchin B, et al. Interleukin 17 acts in synergy with B cell-activating factor to influence B cell biology and the pathophysiology of systemic lupus erythematosus. Nat Immunol. 2009;10(7):778–85. doi:10.1038/ni.1741.

    Article  CAS  PubMed  Google Scholar 

  6. Yang XO, Chang SH, Park H, Nurieva R, Shah B, Acero L, et al. Regulation of inflammatory responses by IL-17F. J Exp Med. 2008;205(5):1063–75. doi:10.1084/jem.20071978.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Wang L, Jiang Y, Zhang Y, Wang Y, Huang S, Wang Z, et al. Association analysis of IL-17A and IL-17F polymorphisms in Chinese Han women with breast cancer. PLoS One. 2012;7(3):e34400. doi:10.1371/journal.pone.0034400.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Melton AC, Melrose J, Alajoki L, Privat S, Cho H, Brown N, et al. Regulation of IL-17A production is distinct from IL-17F in a primary human cell co-culture model of T cell-mediated B cell activation. PLoS One. 2013;8(3):e58966. doi:10.1371/journal.pone.0058966.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Numasaki M, Fukushi J, Ono M, Narula SK, Zavodny PJ, Kudo T, et al. Interleukin-17 promotes angiogenesis and tumor growth. Blood. 2003;101(7):2620–7. doi:10.1182/blood-2002-05-1461.

    Article  CAS  PubMed  Google Scholar 

  10. Numasaki M, Watanabe M, Suzuki T, Takahashi H, Nakamura A, McAllister F, et al. IL-17 enhances the net angiogenic activity and in vivo growth of human non-small cell lung cancer in SCID mice through promoting CXCR-2-dependent angiogenesis. J Immunol. 2005;175(9):6177–89.

    Article  CAS  PubMed  Google Scholar 

  11. Starnes T, Robertson MJ, Sledge G, Kelich S, Nakshatri H, Broxmeyer HE, et al. Cutting edge: IL-17F, a novel cytokine selectively expressed in activated T cells and monocytes, regulates angiogenesis and endothelial cell cytokine production. J Immunol. 2001;167(8):4137–40.

    Article  CAS  PubMed  Google Scholar 

  12. Xie Y, Sheng W, Xiang J, Ye Z, Yang J. Interleukin-17F suppresses hepatocarcinoma cell growth via inhibition of tumor angiogenesis. Cancer Investig. 2010;28(6):598–607. doi:10.3109/07357900903287030.

    Article  CAS  Google Scholar 

  13. Tong Z, Yang XO, Yan H, Liu W, Niu X, Shi Y, et al. A protective role by interleukin-17F in colon tumorigenesis. PLoS One. 2012;7(4):e34959. doi:10.1371/journal.pone.0034959.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Sathish N, Wang X, Yuan Y. Human papillomavirus (HPV)-associated oral cancers and treatment strategies. J Dent Res. 2014;93(7 suppl):29S–36. doi:10.1177/0022034514527969.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Li C, Zhao Y, Zhang W. Increased prevalence of T(H)17 cells in the peripheral blood of patients with head and neck squamous cell carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2011;112(1):81–9. doi:10.1016/j.tripleo.2010.11.032.

    Article  PubMed  Google Scholar 

  16. Iwakura Y, Ishigame H, Saijo S, Nakae S. Functional specialization of interleukin-17 family members. Immunity. 2011;34(2):149–62. doi:10.1016/j.immuni.2011.02.012.

    Article  CAS  PubMed  Google Scholar 

  17. Maniati E, Soper R, Hagemann T. Up for mischief? IL-17/Th17 in the tumour microenvironment. Oncogene. 2010;29(42):5653–62. doi:10.1038/onc.2010.367.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Tartour E, Fossiez F, Joyeux I, Galinha A, Gey A, Claret E, et al. Interleukin 17, a T-cell-derived cytokine, promotes tumorigenicity of human cervical tumors in nude mice. Cancer Res. 1999;59(15):3698–704.

    CAS  PubMed  Google Scholar 

  19. Benevides L, Cardoso CR, Tiezzi DG, Marana HR, Andrade JM, Silva JS. Enrichment of regulatory T cells in invasive breast tumor correlates with the upregulation of IL-17A expression and invasiveness of the tumor. Eur J Immunol. 2013;43(6):1518–28. doi:10.1002/eji.201242951.

    Article  CAS  PubMed  Google Scholar 

  20. Kuang DM, Peng C, Zhao Q, Wu Y, Chen MS, Zheng L. Activated monocytes in peritumoral stroma of hepatocellular carcinoma promote expansion of memory T helper 17 cells. Hepatology. 2010;51(1):154–64. doi:10.1002/hep.23291.

    Article  CAS  PubMed  Google Scholar 

  21. Lv L, Pan K, Li XD, She KL, Zhao JJ, Wang W, et al. The accumulation and prognosis value of tumor infiltrating IL-17 producing cells in esophageal squamous cell carcinoma. PLoS One. 2011;6(3):e18219. doi:10.1371/journal.pone.0018219.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Le Gouvello S, Bastuji-Garin S, Aloulou N, Mansour H, Chaumette MT, Berrehar F, et al. High prevalence of Foxp3 and IL17 in MMR-proficient colorectal carcinomas. Gut. 2008;57(6):772–9. doi:10.1136/gut.2007.123794.

    Article  PubMed  Google Scholar 

  23. Reynolds JM, Angkasekwinai P, Dong C. IL-17 family member cytokines: regulation and function in innate immunity. Cytokine Growth Factor Rev. 2010;21(6):413–23. doi:10.1016/j.cytogfr.2010.10.002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Quan Y, Zhou B, Wang Y, Duan R, Wang K, Gao Q, et al. Association between IL17 polymorphisms and risk of cervical cancer in Chinese women. Clin Dev Immunol. 2012;2012:258293. doi:10.1155/2012/258293.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Wu X, Zeng Z, Chen B, Yu J, Xue L, Hao Y, et al. Association between polymorphisms in interleukin-17A and interleukin-17F genes and risks of gastric cancer. Int J Cancer J Int du Cancer. 2010;127(1):86–92. doi:10.1002/ijc.25027.

    Article  CAS  Google Scholar 

  26. Xu C, Hao K, Yu L, Zhang X. Serum interleukin-17 as a diagnostic and prognostic marker for non-small cell lung cancer. Biomarkers Biochem Indic Expo Response Susceptibility to Chem. 2014;19(4):287–90. doi:10.3109/1354750X.2014.908954.

    CAS  Google Scholar 

  27. Chen X, Wan J, Liu J, Xie W, Diao X, Xu J, et al. Increased IL-17-producing cells correlate with poor survival and lymphangiogenesis in NSCLC patients. Lung Cancer. 2010;69(3):348–54. doi:10.1016/j.lungcan.2009.11.013.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by a grant from the National Natural Science Foundation of China (No. 81402238, 81072213 and 81271698), the Nanjing Medical Science & Research Project (No.YKK11039, YKK13145), Nanjing Medical Young Engineer (QRX113311), National Key Disciplines Constructional Project Funding (Since 2011), Jiangsu Provincial Clinical Medicine of Science and Technology project (Grant No BL2012017), Nanjing Municipal Key Medical Laboratory Constructional Project Funding (Since 2012), and Center of Nanjing Clinical Medicine of tumor project (since 2014).

Authors’ contributions

L.D., YH.N. and YY.H. designed experiments with valuable help from XF.H., EL.H., and QG.H. L.D. performed and analyzed data with valuable help from EL.H. and YJ.X. L.D. and DY.Z. wrote the manuscript. XF.H and B.L. collected surgical specimens; YY.H. and YH.N. oversaw the overall project.

Conflicts of interest

None

Author information

Authors and Affiliations

  1. Central Laboratory of Stomatology, Hospital of Stomatology, and The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, China, 210093

    Liang Ding, Er-Ling Hu, Yu-Jun Xu, Dong-Ya Zhang, Yan-Hong Ni & Ya-Yi Hou

  2. Department of Oral and Maxillofacial Surgery, Institute and Hospital of Stomatology, Nanjing University Medical School, Nanjing Stomatological Hospital, Nanjing, China, 210093

    Xiao-Feng Huang, Bing Li & Qin-Gang Hu

Authors
  1. Liang Ding
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Er-Ling Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yu-Jun Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xiao-Feng Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Dong-Ya Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Bing Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Qin-Gang Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yan-Hong Ni
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Ya-Yi Hou
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Yan-Hong Ni or Ya-Yi Hou.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ding, L., Hu, EL., Xu, YJ. et al. Serum IL-17F combined with VEGF as potential diagnostic biomarkers for oral squamous cell carcinoma. Tumor Biol. 36, 2523–2529 (2015). https://doi.org/10.1007/s13277-014-2867-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-014-2867-z

Keywords

Search

Navigation