Abstract
Foxp3 is a member of the forkhead/ winged helix transcription factor family which is highly expressed in CD4+CD25+ regulatory T cells and was recently identified as a key player in T cells with regulatory potential. We describe the expression and function of Foxp3 in pancreatic ductal adenocarcinoma cell lines and cancer tissue resulting in an inhibition of proliferation of naïve T cells. The expression of Foxp3 in pancreatic cancer cell lines is regulated by TGF-β2 which resembles the mechanisms in regulatory T cells. We detected Foxp3 mRNA and protein expression in different pancreatic cancer cell lines. In 25/39 pancreatic cancer tissues Foxp3 expression was detectable with immunohistochemistry in the tumor cells, but we found no correlation between Foxp3 expression in the tumor cells and tumor stage and overall-survival. In all pancreatic cancer cell lines Foxp3 positive, tumorinfiltrating lymphocytes were detected. Treatment of pancreatic cancer cell lines with TGF-β2 but not TGF-β1 led to an up regulation of Foxp3 mRNA and protein expression. In line with these findings we found that anti-TGF-β2 treatment resulted in Foxp3 down regulation. In co-culture assays of Panc89 cells with naïve T-cells a strong anti-proliferative effect on the proliferation of naïve T-cells was observed. Interestingly, this effect could be partially reverted after inhibition of FoxP3 expression in Panc89 cells, indicating that this suppressive effect is dependent on FoxP3 expression. This demonstrates that regulation of Foxp3 expression in pancreatic cancer cells may be similar to the known pathways in Treg and that pancreatic cancer cells might mimic functions of Treg through Foxp3-dependent suppression of T-cell proliferation.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsLiteratur
Hori S, Nomura T, Sakaguchi S (2003) Control of regulatory T cell development by the transcription factor Foxp3. Science 299: 1057–1061
Khattri R, Cox T, Yasayko SA, Ramsdell F (2003) An essential role for Scurfin in CD4+CD25+ T regulatory cells. Nat Immunol 4: 337–342
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 (2007) FOXP3 is an X-linked breast cancer suppressor gene and an important repressor of the HER-2/ErbB2 oncogene. Cell 129: 1275–1286
Chen W, Jin W, Hardegen N, Lei KJ, Li L, Marinos N, McGrady G, Wahl SM (2003) 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 198: 1875–1886
Fantini MC, Becker C, Monteleone G, Pallone F, Galle PR, Neurath MF (2004) Cutting edge: TGF-beta induces a regulatory phenotype in CD4+CD25-T cells through Foxp3 induction and down-regulation of Smad7. J Immunol 172: 5149–5153
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2008 Springer Medizin Verlag Heidelberg
About this paper
Cite this paper
Hinz, S. et al. (2008). Die Expression von Foxp3 in Pankreascarzinomzelllinien wird durch TGF-β2 funktionell reguliert und vermittelt einen anti-proliferativen Effekt auf naïve T-Zellen. In: Arbogast, R., Schackert, H.K., Bauer, H. (eds) Chirurgisches Forum 2008. Deutsche Gesellschaft für Chirurgie, vol 37. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-78833-1_10
Download citation
DOI: https://doi.org/10.1007/978-3-540-78833-1_10
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-540-78821-8
Online ISBN: 978-3-540-78833-1
eBook Packages: Medicine (German Language)