Volume 24, Issue 4 (7-2020)                   IBJ 2020, 24(4): 214-219 | Back to browse issues page

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Mosayebzadeh Roshan H, Abtahi-Eivary S, Shojaee-Mend H, Mohammadzadeh A, Bahari Sani Z. The Effects of WW2/WW3 Domains of Smurf2 Molecule on CD4+CD25+/CD4+ Proportion in Spleen of 4T1 Tumor Bearing BALB/c Mice. IBJ 2020; 24 (4) :214-219
URL: http://ibj.pasteur.ac.ir/article-1-3041-en.html
Background: TGF-β has long been considered as the main inducer of Tregs in tumor microenvironment and is the reason for the aberrant number of Tregs in tumor-bearing individuals. Recently, it has been suggested that the enzyme arginase I is able to mediate the induction of Tregs in a TGF-β-independent fashion. The recombinant WW2/WW3 domains from smad ubiquitination regulatory factor 2 molecule was demonstrated to increase TGF-β signaling while reducing arginase I gene expression. In this study, we aimed to examine the effects of this recombinant protein on CD4+CD25+/CD4+ proportion in the spleen of 4T1 mammary carcinoma-bearing BALB/c mice. Methods: Flow cytometry was used to evaluate CD4+CD25+ spleen cell populations of the tumor-bearing mice that received WW2/WW3 protein treatment and those of the control group. Results: The results indicated a significant rise in CD4+CD25+/CD4+ ratio, along with an average increase in tumor mass of the subjects that underwent protein treatment. Conclusion: It can be inferred that the heightened CD4+CD25+/CD4+ proportion in the spleen of  protein-treated tumor-bearing mice can be the result of the increased TGF-β signaling despite the reduced arginase I expression. 
Type of Study: Full Length/Original Article | Subject: Related Fields

1. Ghiringhelli F, Puig PE, Roux S, Parcellier A, Schmitt E, Solary E, Kroemer G, Martin F, Chauffert B, Zitvogel L. Tumor cells convert immature myeloid dendritic cells into TGF-beta-secreting cells inducing CD4+CD25+ regulatory T cell proliferation. The journal of experimental medicine 2005; 202(7): 919-929. [DOI:10.1084/jem.20050463]
2. Flavell RA, Sanjabi S, Wrzesinski SH, Licona-Limon P. The polarization of immune cells in the tumour environment by TGFbeta. Nature reviews immunology 2010; 10(8): 554-567. [DOI:10.1038/nri2808]
3. Souza-Fonseca-Guimaraes F, Smyth MJ. Myeloid TGF-beta responsiveness promotes metastases. Cancer discovery 2013; 3(8): 846-848. [DOI:10.1158/2159-8290.CD-13-0271]
4. Sinha P, Clements VK, Fulton AM, Ostrand-Rosenberg S. Prostaglandin E2 promotes tumor progression by inducing myeloid-derived suppressor cells. Cancer research 2007; 67(9): 4507-4513. [DOI:10.1158/0008-5472.CAN-06-4174]
5. Bronte V, Serafini P, De Santo C, Marigo I, Tosello V, Mazzoni A, Segal DM, Staib C, Lowel M, Sutter G, Colombo MP, Zanovello P. IL-4-induced arginase 1 suppresses alloreactive T cells in tumor-bearing mice. Journal of immunology 2003; 170(1): 270-278. [DOI:10.4049/jimmunol.170.1.270]
6. Ochoa AC, Zea AH, Hernandez C, Rodriguez PC. Arginase, prostaglandins, and myeloid-derived suppressor cells in renal cell carcinoma. Clinical cancer research 2007; 13(2 Pt 2): 721s-726s. [DOI:10.1158/1078-0432.CCR-06-2197]
7. Rodriguez PC, Quiceno DG, Zabaleta J, Ortiz B, Zea AH, Piazuelo MB, Delgado A, Correa P, Brayer J, Sotomayor EM, Antonia S, Ochoa JB, Ochoa AC. Arginase I production in the tumor microenvironment by mature myeloid cells inhibits T-cell receptor expression and antigen-specific T-cell responses. Cancer research 2004; 64(16): 5839-5849. [DOI:10.1158/0008-5472.CAN-04-0465]
8. Rodriguez PC, Zea AH, Culotta KS, Zabaleta J, Ochoa JB, Ochoa AC. Regulation of T cell receptor CD3zeta chain expression by L-arginine. The journal of biological chemistry 2002; 277(24): 21123-21129. [DOI:10.1074/jbc.M110675200]
9. Li Z, Pang Y, Gara SK, Achyut BR, Heger C, Goldsmith PK, Lonning S, Yang L. Gr-1+CD11b+ cells are responsible for tumor promoting effect of TGF-beta in breast cancer progression. International journal of cancer 2012; 131(11): 2584-2595. [DOI:10.1002/ijc.27572]
10. Chong PA, Lin H, Wrana JL, Forman-Kay JD. Coupling of tandem Smad ubiquitination regulatory factor (Smurf) WW domains modulates target specificity. Proceedings of the National Academy of Sciences of the United States of America 2010; 107(43): 18404-18409. [DOI:10.1073/pnas.1003023107]
11. Ganji A, Roshan HM, Varasteh A, Moghadam M, Sankian M. The effects of WW2/WW3 domains of Smurf2 molecule on TGF‐β signaling and arginase I gene expression. Cell biology international 2015; 39(6): 690-695. [DOI:10.1002/cbin.10446]
12. Valzasina B, Piconese S, Guiducci C, Colombo MP. Tumor-induced expansion of regulatory T cells by conversion of CD4+CD25- lymphocytes is thymus and proliferation independent. Cancer research 2006; 66(8): 4488-4495. [DOI:10.1158/0008-5472.CAN-05-4217]
13. 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. The journal of experimental medicine 2003; 198(12): 1875-1886. [DOI:10.1084/jem.20030152]
14. Serafini P, Mgebroff S, Noonan K, Borrello I. Myeloid-derived suppressor cells promote cross-tolerance in B-cell lymphoma by expanding regulatory T cells. Cancer research 2008; 68(13): 5439-5449. [DOI:10.1158/0008-5472.CAN-07-6621]
15. Huang B, Pan PY, Li Q, Sato AI, Levy DE, Bromberg J, Divino CM, Chen SH. Gr-1+CD115+ immature myeloid suppressor cells mediate the development of tumor-induced T regulatory cells and T-cell anergy in tumor-bearing host. Cancer research 2006; 66(2): 1123-1131. [DOI:10.1158/0008-5472.CAN-05-1299]
16. Lelekakis M, Moseley JM, Martin TJ, Hards D, Williams E, Ho P, Lowen D, Javni J, Miller FR, Slavin J, Anderson RL. A novel orthotopic model of breast cancer metastasis to bone. Clinical and experimental metastasis 1999; 17(2): 163-170. [DOI:10.1023/A:1006689719505]
17. McEarchern JA, Kobie JJ, Mack V, Wu RS, Meade-Tollin L, Arteaga CL, Dumont N, Besselsen D, Seftor E, Hendrix MJ, Katsanis E, Akporiaye ET. Invasion and metastasis of a mammary tumor involves TGF-beta signaling. International journal of cancer 2001; 91(1): 76-82. https://doi.org/10.1002/1097-0215(20010101)91:1<76::AID-IJC1012>3.0.CO;2-8 [DOI:10.1002/1097-0215(20010101)91:13.0.CO;2-8]
18. Secondini C, Coquoz O, Spagnuolo L, Spinetti T, Peyvandi S, Ciarloni L, Botta F, Bourquin C, Rüegg C. Arginase inhibition suppresses lung metastasis in the 4T1 breast cancer model independently of the immunomodulatory and anti-metastatic effects of VEGFR-2 blockade. Oncoimmunology 2017; 6(6): e1316437. [DOI:10.1080/2162402X.2017.1316437]
19. Whiteside TL. The tumor microenvironment and its role in promoting tumor growth. Oncogene 2008; 27(45): 5904-5912. [DOI:10.1038/onc.2008.271]
20. Lindau D, Gielen P, Kroesen M, Wesseling P, Adema GJ. The immunosuppressive tumour network: myeloid-derived suppressor cells, regulatory T cells and natural killer T cells. Immunology 2013; 138(2): 105-115. [DOI:10.1111/imm.12036]
21. Liu JY, Zhang XS, Ding Y, Peng RQ, Cheng X, Zhang NH, Xia JC, Zeng YX. The changes of CD4+CD25+/CD4+ proportion in spleen of tumor-bearing BALB/c mice. Journal of translational medicine 2005; 3(1): 5. [DOI:10.1186/1479-5876-3-5]
22. Sasada T, Kimura M, Yoshida Y, Kanai M, Takabayashi A. CD4+CD25+ regulatory T cells in patients with gastrointestinal malignancies: possible involvement of regulatory T cells in disease progression. Cancer 2003; 98(5): 1089-1099. [DOI:10.1002/cncr.11618]
23. Dzik JM. Evolutionary roots of arginase expression and regulation. Frontiers in immunology 2014; 5: 544. [DOI:10.3389/fimmu.2014.00544]
24. Munder M. Arginase: an emerging key player in the mammalian immune system. British journal of pharmacology 2009; 158(3): 638-651. [DOI:10.1111/j.1476-5381.2009.00291.x]
25. Bronte V, Zanovello P. Regulation of immune responses by L-arginine metabolism. Nature reviews Immunology 2005; 5(8): 641-654. [DOI:10.1038/nri1668]
26. Liu Z, Kim JH, Falo LD, Jr., You Z. Tumor regulatory T cells potently abrogate antitumor immunity. Journal of immunology 2009; 182(10): 6160-6167. [DOI:10.4049/jimmunol.0802664]

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