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Clinical significance of FOXP3 expression in human gliomas

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Abstract

Objective

Studies have demonstrated that the transcription factor forkhead box P3 (FOXP3) is expressed not only in regulatory T cells, but also in some cancer cells. This study aims to clarify whether or not FOXP3 expression occurs in human gliomas and investigate the clinical significance of this expression in gliomas.

Methods

We detected FOXP3 protein expression in 40 glioma samples, 3 normal brain tissue samples, and 4 normal tonsil tissue samples using immunohistochemical staining and western blot. The expression of FOXP3 protein was also detected in five glioma cell lines by western blot. We also evaluated the association of FOXP3 expression with clinical pathological grades, prognosis, and recurrence.

Results

Western blot analysis showed that the expression of FOXP3 protein was upregulated in high-grade glioma (HGGS) samples compared with low-grade samples. The cell line U87 showed the highest FOXP3 expression, while U373 had the lowest expression. Immunohistochemical analysis detected FOXP3 protein in 35 out of the 40 (87.5 %) glioma samples and high levels of FOXP3 were observed in 26 out of the 27 (96.3 %) high-grade gliomas samples. Statistical analysis suggested that the upregulation of FOXP3 is significantly correlated with the histologic grade of gliomas (P < 0.05) and that patients with high expression of FOXP3 protein exhibit a poorer prognosis than those with low FOXP3 expression.

Conclusions

Our findings suggest that FOXP3 expression in glioma cells has a crucial function in the development of HGGS and is associated with the malignant biological behavior of HGGS.

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References

  1. Fontenot JD, Rasmussen JP, Williams LM, Dooley JL, Farr AG, Rudensky AY. Regulatory T cell lineage specification by the forkhead transcription factor Foxp3. Immunity. 2005;22:329–41.

    Article  CAS  PubMed  Google Scholar 

  2. Chen W, Jin W, Hardegen N, Lei KJ, Li L, Marinos N, McGrady G, Wahl SM. Conversion of peripheral CD4+CD25− naive T cells to CD4+CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3. J Exp Med. 2003;198:1875–86.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Hinz S, Pagerols-Raluy L, Oberg HH, Ammerpohl O, Grussel S, Sipos B, Grutzmann R, Pilarsky C, Ungefroren H, Saeger HD, Kloppel G, Kabelitz D, Kalthoff H. Foxp3 expression in pancreatic carcinoma cells as a novel mechanism of immune evasion in cancer. Cancer Res. 2007;67:8344–50.

    Article  CAS  PubMed  Google Scholar 

  4. Zuo T, Wang L, Morrison C, Chang X, Zhang H, Li W, Liu Y, Wang Y, Liu X, Chan MW, Liu JQ, Love R, Liu CG, Godfrey V, Shen R, Huang TH, Yang T, Park BK, Wang CY, Zheng P, Liu Y. FOXP3 is an X-linked breast cancer suppressor gene and an important repressor of the HER-2/ErbB2 oncogene. Cell. 2007;129:1275–86.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. Ebert LM, Tan BS, Browning J, Svobodova S, Russell SE, Kirkpatrick N, Gedye C, Moss D, Ng SP, MacGregor D, Davis ID, Cebon J, Chen W. The regulatory T cell-associated transcription factor FoxP3 is expressed by tumor cells. Cancer Res. 2008;68:3001–9.

    Article  CAS  PubMed  Google Scholar 

  6. Wang LH, Su L, Wang JT. Correlation between elevated FOXP3 expression and increased lymph node metastasis of gastric cancer. Chin Med J (Engl). 2010;123:3545–9.

    CAS  Google Scholar 

  7. Darefsky AS, King JT Jr, Dubrow R. Adult glioblastoma multiforme survival in the temozolomide era: a population-based analysis of surveillance, epidemiology, and end results registries. Cancer. 2012;118:2163–72.

    Article  PubMed Central  PubMed  Google Scholar 

  8. Walbert T, Mikkelsen T. Recurrent high-grade glioma: a diagnostic and therapeutic challenge. Expert Rev Neurother. 2011;11:509–18.

    Article  PubMed  Google Scholar 

  9. Sadones J, Michotte A, Veld P, Chaskis C, Sciot R, Menten J, Joossens EJ, Strauven T, D’Hondt LA, Sartenaer D, Califice SF, Bierau K, Svensson C, De Greve J, Neyns B. MGMT promoter hypermethylation correlates with a survival benefit from temozolomide in patients with recurrent anaplastic astrocytoma but not glioblastoma. Eur J Cancer. 2009;45:146–53.

    Article  CAS  PubMed  Google Scholar 

  10. Adams H, Avendano J, Raza SM, Gokaslan ZL, Jallo GI, Quinones-Hinojosa A. Prognostic factors and survival in primary malignant astrocytomas of the spinal cord: a population-based analysis from 1973 to 2007. Spine (Phila Pa 1976) 2012; 37:E727–35.

  11. Wainwright DA, Sengupta S, Han Y, Ulasov IV, Lesniak MS. The presence of IL-17A and T helper 17 cells in experimental mouse brain tumors and human glioma. PLoS One. 2010;5:e15390.

    Article  PubMed Central  PubMed  Google Scholar 

  12. Zhang B, Feng X, Wang J, Xu X, Liu H, Lin N. Adenovirus-mediated delivery of bFGF small interfering RNA increases levels of connexin 43 in the glioma cell line, U251. J Exp Clin Cancer Res. 2010;29:3.

    Article  PubMed  Google Scholar 

  13. Zhang B, Feng X, Wang J, Xu X, Lin N, Liu H. Combined antitumor effect of Ad-bFGF-siRNA and Ad-Vpr on the growth of xenograft glioma in nude mouse model. Pathol Oncol Res. 2011;17:237–42.

    Article  PubMed  Google Scholar 

  14. Karanikas V, Speletas M, Zamanakou M, Kalala F, Loules G, Kerenidi T, Barda AK, Gourgoulianis KI, Germenis AE. Foxp3 expression in human cancer cells. J Transl Med. 2008;6:19.

    Article  PubMed Central  PubMed  Google Scholar 

  15. Wang L, Liu R, Li W, Chen C, Katoh H, Chen GY, McNally B, Lin L, Zhou P, Zuo T, Cooney KA, Liu Y, Zheng P. Somatic single hits inactivate the X-linked tumor suppressor FOXP3 in the prostate. Cancer Cell. 2009;16:336–46.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Zuo T, Liu R, Zhang H, Chang X, Liu Y, Wang L, Zheng P, Liu Y. FOXP3 is a novel transcriptional repressor for the breast cancer oncogene SKP2. J Clin Invest. 2007;117:3765–73.

    CAS  PubMed Central  PubMed  Google Scholar 

  17. Jung DJ, Jin DH, Hong SW, Kim JE, Shin JS, Kim D, Cho BJ, Hwang YI, Kang JS, Lee WJ. Foxp3 expression in p53-dependent DNA damage responses. J Biol Chem. 2010;285:7995–8002.

    Article  CAS  PubMed  Google Scholar 

  18. Cunha LL, Morari EC, Nonogaki S, Soares FA, Vassallo J, Ward LS. Foxp3 expression is associated with aggressiveness in differentiated thyroid carcinomas. Clinics (Sao Paulo). 2012;67:483–8.

    Article  Google Scholar 

  19. Heimberger AB, Abou-Ghazal M, Reina-Ortiz C, Yang DS, Sun W, Qiao W, Hiraoka N, Fuller GN. Incidence and prognostic impact of FoxP3+ regulatory T cells in human gliomas. Clin Cancer Res. 2008;14:5166–72.

    Article  CAS  PubMed  Google Scholar 

  20. Held-Feindt J, Hattermann K, Sebens S, Krautwald S, Mehdorn HM, Mentlein R. The transcription factor forkhead box P3 (FoxP3) is expressed in glioma cells and associated with increased apoptosis. Exp Cell Res. 2013;319:731–9.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by the grant from the Tianjin Science and Technology Committee (11JCYBJC12100, 12ZCDZSY17700), the National Natural Science Foundation of China (81101911), the Tianjin Health Bureau Science and Technique Foundation (11KG115), and State Key Clinical Department of Neurosurgery.

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Graduate School, Tianjin Medical University, No. 22 Qixiangtai Road, Tianjin, 300070, China

    L. Wang & S. Zhang

  2. Tianjin Neurosurgical Institute, Tianjin Huanhu Hospital, 122# Qixiangtai Road, Tianjin, 300060, China

    L. Wang, S. Zhang & J. Wang

  3. Clinical Laboratory, Tianjin Huanhu Hospital, 122# Qixiangtai Road, Tianjin, 300060, China

    B. Zhang

  4. Key Laboratory for Critical Care Medicine of the Ministry of Health, Tianjin First Center Hospital, No. 24 Fukang Road, Tianjin, 300192, China

    X. Xu & X. Feng

  5. Department of Pathology, Tianjin Huanhu Hospital, 122# Qixiangtai Road, Tianjin, 300060, China

    X. Yan & F. Kong

  6. Department of Neurosurgery, Tianjin Huanhu Hospital, 122# Qixiangtai Road, Tianjin, 300060, China

    J. Wang

Authors
  1. L. Wang
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  2. B. Zhang
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  3. X. Xu
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  4. S. Zhang
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  5. X. Yan
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  6. F. Kong
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  7. X. Feng
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  8. J. Wang
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Corresponding author

Correspondence to J. Wang.

Additional information

L. Wang and B. Zhang contributed equally to this work and should be considered as co-first authors.

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Wang, L., Zhang, B., Xu, X. et al. Clinical significance of FOXP3 expression in human gliomas. Clin Transl Oncol 16, 36–43 (2014). https://doi.org/10.1007/s12094-013-1037-x

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  • DOI: https://doi.org/10.1007/s12094-013-1037-x

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