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Foxp3 expression in human cancer cells.

Karanikas V, Speletas M, Zamanakou M, Kalala F, Loules G, Kerenidi T, Barda AK, Gourgoulianis KI, Germenis AE - J Transl Med (2008)

Bottom Line: Limited evidence indicates that it is also expressed, albeit to a lesser extent, in tissues other than thymus and spleen, while, very recently, it was shown that Foxp3 is expressed by pancreatic carcinoma.This expression correlated with the expression levels of IL-10 and TGFb1.The biological significance of these findings warrants further investigation in the context of tumor immune escape, and especially under the light of current anti-cancer efforts interfering with Foxp3 expression.

View Article: PubMed Central - HTML - PubMed

Affiliation: Cancer Immunology Unit, Department of Immunology and Histocompatibility, School of Medicine, University of Thessaly, University Hospital of Larissa, GR-411 10 Larissa, Greece. vkaran@med.uth.gr

ABSTRACT

Objective: Transcription factor forkhead box protein 3 (Foxp3) specifically characterizes the thymically derived naturally occurring regulatory T cells (Tregs). Limited evidence indicates that it is also expressed, albeit to a lesser extent, in tissues other than thymus and spleen, while, very recently, it was shown that Foxp3 is expressed by pancreatic carcinoma. This study was scheduled to investigate whether expression of Foxp3 transcripts and mature protein occurs constitutively in various tumor types.

Materials and methods: Twenty five tumor cell lines of different tissue origins (lung cancer, colon cancer, breast cancer, melanoma, erythroid leukemia, acute T-cell leukemia) were studied. Detection of Foxp3 mRNA was performed using both conventional RT-PCR and quantitative real-time PCR while protein expression was assessed by immunocytochemistry and flow cytometry, using different antibody clones.

Results: Foxp3 mRNA as well as Foxp3 protein was detected in all tumor cell lines, albeit in variable levels, not related to the tissue of origin. This expression correlated with the expression levels of IL-10 and TGFb1.

Conclusion: We offer evidence that Foxp3 expression, characterizes tumor cells of various tissue origins. The biological significance of these findings warrants further investigation in the context of tumor immune escape, and especially under the light of current anti-cancer efforts interfering with Foxp3 expression.

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Immunohistochemical staining of tumor cell line cytospins. A: Melanoma (GERL); predominant cytoplasmic expression. B: Lung adenocarcinoma (GILI); cytoplasmic and nuclear expression. C: Colon adenocarcinoma (HCA 2.6); predominant cytoplasmic expression. D: T Lymphoblastic leukemia (JURKAT); cytoplasmic and nuclear expression. E: Breast adenocarcinoma (MCF7); predominant cytoplasmic expression. F: Not expressing EBV-transformed B cells. Inserts represent May-Gruvald-Giemsa staining of the corresponding cell lines.
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Figure 2: Immunohistochemical staining of tumor cell line cytospins. A: Melanoma (GERL); predominant cytoplasmic expression. B: Lung adenocarcinoma (GILI); cytoplasmic and nuclear expression. C: Colon adenocarcinoma (HCA 2.6); predominant cytoplasmic expression. D: T Lymphoblastic leukemia (JURKAT); cytoplasmic and nuclear expression. E: Breast adenocarcinoma (MCF7); predominant cytoplasmic expression. F: Not expressing EBV-transformed B cells. Inserts represent May-Gruvald-Giemsa staining of the corresponding cell lines.

Mentions: All tumor lines tested, exhibited distinct staining profiles (Fig. 2). Heterogenous subcellular localization of Foxp3 (predominantly perinuclear cytoplasmic and/or mainly nuclear) was observed in lines of epithelial as well as of non-epithelial origin, while EBV-transformed B cells were devoid of staining. This finding warrants further attention with respect to the possible functional consequences of nuclear and/or perinuclear cytoplasmic Foxp3 expression by cancer cells. In particular, under the light of recent findings revealing the physical interaction of Foxp3 with the nuclear factor of activated T cells (NFAT), it appears that at least with respect to its nuclear localization, Foxp3 plays a pivotal role in the formation of nuclear complexes that are important to regulate the transcription of several target genes [16], that confer to Tregs their suppressive function [17].


Foxp3 expression in human cancer cells.

Karanikas V, Speletas M, Zamanakou M, Kalala F, Loules G, Kerenidi T, Barda AK, Gourgoulianis KI, Germenis AE - J Transl Med (2008)

Immunohistochemical staining of tumor cell line cytospins. A: Melanoma (GERL); predominant cytoplasmic expression. B: Lung adenocarcinoma (GILI); cytoplasmic and nuclear expression. C: Colon adenocarcinoma (HCA 2.6); predominant cytoplasmic expression. D: T Lymphoblastic leukemia (JURKAT); cytoplasmic and nuclear expression. E: Breast adenocarcinoma (MCF7); predominant cytoplasmic expression. F: Not expressing EBV-transformed B cells. Inserts represent May-Gruvald-Giemsa staining of the corresponding cell lines.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2386447&req=5

Figure 2: Immunohistochemical staining of tumor cell line cytospins. A: Melanoma (GERL); predominant cytoplasmic expression. B: Lung adenocarcinoma (GILI); cytoplasmic and nuclear expression. C: Colon adenocarcinoma (HCA 2.6); predominant cytoplasmic expression. D: T Lymphoblastic leukemia (JURKAT); cytoplasmic and nuclear expression. E: Breast adenocarcinoma (MCF7); predominant cytoplasmic expression. F: Not expressing EBV-transformed B cells. Inserts represent May-Gruvald-Giemsa staining of the corresponding cell lines.
Mentions: All tumor lines tested, exhibited distinct staining profiles (Fig. 2). Heterogenous subcellular localization of Foxp3 (predominantly perinuclear cytoplasmic and/or mainly nuclear) was observed in lines of epithelial as well as of non-epithelial origin, while EBV-transformed B cells were devoid of staining. This finding warrants further attention with respect to the possible functional consequences of nuclear and/or perinuclear cytoplasmic Foxp3 expression by cancer cells. In particular, under the light of recent findings revealing the physical interaction of Foxp3 with the nuclear factor of activated T cells (NFAT), it appears that at least with respect to its nuclear localization, Foxp3 plays a pivotal role in the formation of nuclear complexes that are important to regulate the transcription of several target genes [16], that confer to Tregs their suppressive function [17].

Bottom Line: Limited evidence indicates that it is also expressed, albeit to a lesser extent, in tissues other than thymus and spleen, while, very recently, it was shown that Foxp3 is expressed by pancreatic carcinoma.This expression correlated with the expression levels of IL-10 and TGFb1.The biological significance of these findings warrants further investigation in the context of tumor immune escape, and especially under the light of current anti-cancer efforts interfering with Foxp3 expression.

View Article: PubMed Central - HTML - PubMed

Affiliation: Cancer Immunology Unit, Department of Immunology and Histocompatibility, School of Medicine, University of Thessaly, University Hospital of Larissa, GR-411 10 Larissa, Greece. vkaran@med.uth.gr

ABSTRACT

Objective: Transcription factor forkhead box protein 3 (Foxp3) specifically characterizes the thymically derived naturally occurring regulatory T cells (Tregs). Limited evidence indicates that it is also expressed, albeit to a lesser extent, in tissues other than thymus and spleen, while, very recently, it was shown that Foxp3 is expressed by pancreatic carcinoma. This study was scheduled to investigate whether expression of Foxp3 transcripts and mature protein occurs constitutively in various tumor types.

Materials and methods: Twenty five tumor cell lines of different tissue origins (lung cancer, colon cancer, breast cancer, melanoma, erythroid leukemia, acute T-cell leukemia) were studied. Detection of Foxp3 mRNA was performed using both conventional RT-PCR and quantitative real-time PCR while protein expression was assessed by immunocytochemistry and flow cytometry, using different antibody clones.

Results: Foxp3 mRNA as well as Foxp3 protein was detected in all tumor cell lines, albeit in variable levels, not related to the tissue of origin. This expression correlated with the expression levels of IL-10 and TGFb1.

Conclusion: We offer evidence that Foxp3 expression, characterizes tumor cells of various tissue origins. The biological significance of these findings warrants further investigation in the context of tumor immune escape, and especially under the light of current anti-cancer efforts interfering with Foxp3 expression.

Show MeSH
Related in: MedlinePlus