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Open Access 01-12-2016 | Research

Wilms’ tumor susceptibility: possible involvement of FOXP3 and CXCL12 genes

Authors: Patricia Midori Murobushi Ozawa, Carolina Batista Ariza, Roberta Losi-Guembarovski, Alda Losi Guembarovski, Carlos Eduardo Coral de Oliveira, Bruna Karina Banin-Hirata, Marina Okuyama Kishima, Diego Lima Petenuci, Maria Angelica Ehara Watanabe

Published in: Molecular and Cellular Pediatrics | Issue 1/2016

Abstract

Background

Wilms’ tumor is an embryonal neoplasm of the kidney that accounts for approximately 6 % of all childhood tumors. The chemokine CXCL12 (C-X-C chemokine ligand 12) and its ligand CXCR4 (C-X-C chemokine receptor type 4) are involved in the development of several organs, including the kidney, and are also associated with tumor growth and metastasis. FOXP3 (forkhead transcription factor 3) was initially described as a marker for regulatory T cells; however, its expression in several types of tumor cells has already been described and may have prognostic significance. The aim of the present study was to analyze rs3761548 and rs2232365 FOXP3 polymorphisms, as well as evaluate rs1801157 CXCL12 polymorphism in Wilms’ tumor samples.

Methods

Polymorphisms were evaluated in 32 patients and 78 neoplasia-free controls. Genotypes of rs1801157 were determined using PCR-restriction fragment length polymorphism (PCR-RFLP) method, and genotypes of rs2232365 and rs3761548 were determined using allele-specific PCR (AS-PCR).

Results

The case-control study indicated a significant association for allele A carriers of rs1801157 polymorphism in relation to Wilms’ tumor susceptibility (OR = 5.261; 95 % CI 2.156 to 12.84; p = 0.0002). The opposite was observed in male carriers of G allele for rs2232365 polymorphism (OR 0.1164; 95 % CI 0.0227 to 0.5954; p = 0.0091) or when male and female subjects were analyzed (OR = 0.1304; 95 % CI 0.05013 to 0.3394; p < 0.0001).

Conclusions

All in all, these markers may contribute to this neoplasia susceptibility and progression; however, further studies are needed to real clarify their role in Wilms’ tumor pathogenesis.

Malkin D (1997) Cancer of childhood. In: Vita VT Jr, Hellman S, Rosenberg SA (eds) Cancer: principles and practice of oncology, 5th edn. Lippincott-Raven, New York

Davidoff AM (2012) Wilms tumor. Adv Pediatr 59:247–267. doi:10.1016/j.yapd.2012.04.001 CrossRefPubMedPubMedCentral

Beckwith JB (1994) Renal pathology with clinical and functional correlations. J B. Lippincott Company, Philadelphia

Ries L, Eisner M, Kosary C, Hankey B, Miller B, Clegg L et al (2004) SEER cancer statistics review, 1975-2001. National Cancer Institute, Bethesda, http://seer.cancer.gov/csr/1975_2001/

Breslow NE, Beckwith JB, Perlman EJ, Reeve AE (2006) Age distributions, birth weights, nephrogenic rests, and heterogeneity in the pathogenesis of Wilms tumor. Pediatr Blood Cancer 47:260–267. doi:10.1002/pbc.20891 CrossRefPubMedPubMedCentral

Yaqub S, Aandahl EM (2009) Inflammation versus adaptive immunity in cancer pathogenesis. Crit Rev Oncog 15:43–63CrossRefPubMed

Fridman WH, Galon J, Dieu-Nosjean MC, Cremer I, Fisson S, Damotte D et al (2011) Immune infiltration in human cancer: prognostic significance and disease control. Curr Top Microbiol Immunol 344:1–24. doi:10.1007/82_2010_46 PubMed

Viola A, Luster AD (2008) Chemokines and their receptors: drug targets in immunity and inflammation. Annu Rev Pharmacol Toxicol 48:171–197. doi:10.1146/annurev.pharmtox.48.121806.154841 CrossRefPubMed

Balkwill F (2003) Chemokine biology in cancer. Semin Immunol 15:49–55CrossRefPubMed

10.

Klein RS, Rubin JB, Gibson HD, DeHaan EN, Alvarez-Hernandez X, Segal RA et al (2001) SDF-1 alpha induces chemotaxis and enhances Sonic hedgehog-induced proliferation of cerebellar granule cells. Development 128:1971–1981PubMed

11.

Nagasawa T, Tachibana K, Kishimoto T (1998) A novel CXC chemokine PBSF/SDF-1 and its receptor CXCR4: their functions in development, hematopoiesis and HIV infection. Semin Immunol 10:179–185. doi:10.1006/smim.1998.0128 CrossRefPubMed

12.

Salcedo R, Oppenheim JJ (2003) Role of chemokines in angiogenesis: CXCL12/SDF-1 and CXCR4 interaction, a key regulator of endothelial cell responses. Microcirculation 10:359–370. doi:10.1038/sj.mn.7800200 CrossRefPubMed

13.

Takabatake Y, Sugiyama T, Kohara H, Matsusaka T, Kurihara H, Koni PA et al (2009) The CXCL12 (SDF-1)/CXCR4 axis is essential for the development of renal vasculature. J Am Soc Nephrol 20:1714–1723. doi:10.1681/ASN.2008060640 CrossRefPubMedPubMedCentral

14.

Orimo A, Gupta PB, Sgroi DC, Arenzana-Seisdedos F, Delaunay T, Naeem R et al (2005) Stromal fibroblasts present in invasive human breast carcinomas promote tumor growth and angiogenesis through elevated SDF-1/CXCL12 secretion. Cell 121:335–348. doi:10.1016/j.cell.2005.02.034 CrossRefPubMed

15.

Muller A, Homey B, Soto H, Ge N, Catron D, Buchanan ME et al (2001) Involvement of chemokine receptors in breast cancer metastasis. Nature 410:50–56. doi:10.1038/35065016 CrossRefPubMed

16.

de Lourdes PA, Guembarovski RL, Oda JM, Lopes LF, Ariza CB, Amarante MK et al (2013) CXCL12 and TP53 genetic polymorphisms as markers of susceptibility in a Brazilian children population with acute lymphoblastic leukemia (ALL). Mol Biol Rep 40:4591–4596. doi:10.1007/s11033-013-2551-1 CrossRef

17.

Coffer PJ, Burgering BM (2004) Forkhead-box transcription factors and their role in the immune system. Nat Rev Immunol 4:889–899. doi:10.1038/nri1488 CrossRefPubMed

18.

Hori S, Nomura T, Sakaguchi S (2003) Control of regulatory T cell development by the transcription factor Foxp3. Science 299:1057–1061. doi:10.1126/science.1079490 CrossRefPubMed

19.

Ebert LM, Tan BS, Browning J, Svobodova S, Russell SE, Kirkpatrick N et al (2008) The regulatory T cell-associated transcription factor FoxP3 is expressed by tumor cells. Cancer Res 68:3001–3009. doi:10.1158/0008-5472.CAN-07-5664 CrossRefPubMed

20.

Karanikas V, Speletas M, Zamanakou M, Kalala F, Loules G, Kerenidi T et al (2008) Foxp3 expression in human cancer cells. J Transl Med 6:19. doi:10.1186/1479-5876-6-19 CrossRefPubMedPubMedCentral

21.

Zuo T, Wang L, Morrison C, Chang X, Zhang H, Li W et al (2007) FOXP3 is an X-linked breast cancer suppressor gene and an important repressor of the HER-2/ErbB2 oncogene. Cell 129:1275–1286. doi:10.1016/j.cell.2007.04.034 CrossRefPubMedPubMedCentral

22.

Takenaka M, Seki N, Toh U, Hattori S, Kawahara A, Yamaguchi T et al (2013) FOXP3 expression in tumor cells and tumor-infiltrating lymphocytes is associated with breast cancer prognosis. Mol Clin Oncol 1:625–632. doi:10.3892/mco.2013.107 PubMedPubMedCentral

23.

Gao L, Li K, Li F, Li H, Liu L, Wang L et al (2010) Polymorphisms in the FOXP3 gene in Han Chinese psoriasis patients. J Dermatol Sci 57:51–56. doi:10.1016/j.jdermsci.2009.09.010 CrossRefPubMed

24.

Lopes LF, Guembarovski RL, Guembarovski AL, Kishima MO, Campos CZ, Oda JM et al (2014) FOXP3 transcription factor: a candidate marker for susceptibility and prognosis in triple negative breast cancer. Biomed Res Int 2014:341654. doi:10.1155/2014/341654 PubMed

25.

Song P, Wang XW, Li HX, Li K, Liu L, Wei C et al (2013) Association between FOXP3 polymorphisms and vitiligo in a Han Chinese population. Br J Dermatol 169:571–578. doi:10.1111/bjd.12377 CrossRefPubMed

26.

Douglass S, Meeson AP, Overbeck-Zubrzycka D, Brain JG, Bennett MR, Lamb CA et al (2014) Breast cancer metastasis: demonstration that FOXP3 regulates CXCR4 expression and the response to CXCL12. J Pathol 234:74–85. doi:10.1002/path.4381 CrossRefPubMed

27.

Winkler C, Modi W, Smith MW, Nelson GW, Wu X, Carrington M et al (1998) Genetic restriction of AIDS pathogenesis by an SDF-1 chemokine gene variant. ALIVE Study, Hemophilia Growth and Development Study (HGDS), Multicenter AIDS Cohort Study (MACS), Multicenter Hemophilia Cohort Study (MHCS), San Francisco City Cohort (SFCC). Science 279:389–393CrossRefPubMed

28.

Li CM, Guo M, Borczuk A, Powell CA, Wei M, Thaker HM et al (2002) Gene expression in Wilms’ tumor mimics the earliest committed stage in the metanephric mesenchymal-epithelial transition. Am J Pathol 160:2181–2190. doi:10.1016/S0002-9440(10)61166-2 CrossRefPubMedPubMedCentral

29.

Li W, Kessler P, Williams BR (2005) Transcript profiling of Wilms tumors reveals connections to kidney morphogenesis and expression patterns associated with anaplasia. Oncogene 24:457–468. doi:10.1038/sj.onc.1208228 CrossRefPubMed

30.

Ueland J, Yuan A, Marlier A, Gallagher AR, Karihaloo A (2009) A novel role for the chemokine receptor Cxcr4 in kidney morphogenesis: an in vitro study. Dev Dyn 238:1083–1091. doi:10.1002/dvdy.21943 CrossRefPubMed

31.

Grone HJ, Cohen CD, Grone E, Schmidt C, Kretzler M, Schlondorff D et al (2002) Spatial and temporally restricted expression of chemokines and chemokine receptors in the developing human kidney. J Am Soc Nephrol 13:957–967PubMed

32.

Ding M, Cui S, Li C, Jothy S, Haase V, Steer BM et al (2006) Loss of the tumor suppressor Vhlh leads to upregulation of Cxcr4 and rapidly progressive glomerulonephritis in mice. Nat Med 12:1081–1087. doi:10.1038/nm1460 CrossRefPubMed

33.

de Oliveira CE, Cavassin GG, Perim Ade L, Nasser TF, de Oliveira KB, Fungaro MH et al (2007) Stromal cell-derived factor-1 chemokine gene variant in blood donors and chronic myelogenous leukemia patients. J Clin Lab Anal 21:49–54. doi:10.1002/jcla.20142 CrossRefPubMed

34.

de Oliveira KB, Guembarovski RL, Guembarovski AM, da Silva do Amaral Herrera AC, Sobrinho WJ, Ariza CB et al (2013) CXCL12, CXCR4 and IFNgamma genes expression: implications for proinflammatory microenvironment of breast cancer. Clin Exp Med 13:211–219. doi:10.1007/s10238-012-0194-5 CrossRefPubMed

35.

de Oliveira KB, Oda JM, Voltarelli JC, Nasser TF, Ono MA, Fujita TC et al (2009) CXCL12 rs1801157 polymorphism in patients with breast cancer, Hodgkin’s lymphoma, and non-Hodgkin’s lymphoma. J Clin Lab Anal 23:387–393. doi:10.1002/jcla.20346 CrossRefPubMed

36.

Hirata H, Hinoda Y, Kikuno N, Kawamoto K, Dahiya AV, Suehiro Y et al (2007) CXCL12 G801A polymorphism is a risk factor for sporadic prostate cancer susceptibility. Clin Cancer Res 13:5056–5062. doi:10.1158/1078-0432.CCR-07-0859 CrossRefPubMed

37.

Fontenot JD, Gavin MA, Rudensky AY (2003) Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat Immunol 4:330–336, http://www.nature.com/ni/journal/v4/n4/suppinfo/ni904_S1.html CrossRefPubMed

38.

Li W, Wang L, Katoh H, Liu R, Zheng P, Liu Y (2011) Identification of a tumor suppressor relay between the FOXP3 and the Hippo pathways in breast and prostate cancers. Cancer Res 71:2162–2171. doi:10.1158/0008-5472.can-10-3268 CrossRefPubMedPubMedCentral

39.

Zhu J, Yamane H, Cote-Sierra J, Guo L, Paul WE (2006) GATA-3 promotes Th2 responses through three different mechanisms: induction of Th2 cytokine production, selective growth of Th2 cells and inhibition of Th1 cell-specific factors. Cell Res 16:3–10CrossRefPubMed

40.

Wu Z, You Z, Zhang C, Li Z, Su X, Zhang X et al (2012) Association between functional polymorphisms of Foxp3 gene and the occurrence of unexplained recurrent spontaneous abortion in a Chinese Han population. Clin Dev Immunol 2012:896458. doi:10.1155/2012/896458 PubMed

41.

DeNardo DG, Coussens LM (2007) Inflammation and breast cancer. Balancing immune response: crosstalk between adaptive and innate immune cells during breast cancer progression. Breast Cancer Res 9:212–222. doi:10.1186/bcr1746 CrossRefPubMedPubMedCentral

42.

Ellyard JI, Simson L, Parish CR (2007) Th2-mediated anti-tumour immunity: friend or foe? Tissue Antigens 70:1–11. doi:10.1111/j.1399-0039.2007.00869.x CrossRefPubMed

43.

Hinz S, Pagerols-Raluy L, Oberg HH, Ammerpohl O, Grussel S, Sipos B et al (2007) Foxp3 expression in pancreatic carcinoma cells as a novel mechanism of immune evasion in cancer. Cancer Res 67:8344–8350. doi:10.1158/0008-5472.CAN-06-3304 CrossRefPubMed

44.

Zou W (2006) Regulatory T cells, tumour immunity and immunotherapy. Nat Rev Immunol 6:295–307. doi:10.1038/nri1806 CrossRefPubMed

Title: Wilms’ tumor susceptibility: possible involvement of FOXP3 and CXCL12 genes
Authors: Patricia Midori Murobushi Ozawa
Carolina Batista Ariza
Roberta Losi-Guembarovski
Alda Losi Guembarovski
Carlos Eduardo Coral de Oliveira
Bruna Karina Banin-Hirata
Marina Okuyama Kishima
Diego Lima Petenuci
Maria Angelica Ehara Watanabe
Publication date: 01-12-2016
Publisher: Springer Berlin Heidelberg
Published in: Molecular and Cellular Pediatrics / Issue 1/2016
Electronic ISSN: 2194-7791
DOI: https://doi.org/10.1186/s40348-016-0064-4

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Wilms’ tumor susceptibility: possible involvement of FOXP3 and CXCL12 genes

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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