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Toll-like receptor 4 and breast cancer: an updated systematic review

  • Morteza Khademalhosseini
  • Mohammad Kazemi ArababadiEmail author
Review Article

Abstract

Toll-like receptors (TLRs) may play dual roles in human cancers. TLR4 is a key molecule which may participate in both friend and foe roles against breast cancer. This review article collected recent data regarding the mechanisms used by TLR4 in the eradication of breast cancer cells and induction of the tumor cells, and discussed the mechanisms involved in the various functions of TLR4. The literature searches revealed that TLR4 is a key molecule that participates in breast cancer cell eradication or induction of breast cancer development and also transformation of the normal cells. TLR4 eradicates breast cancer cells via recognition of their DAMPs and then induces immune responses. Over-expression of TLR4 and also alterations in its signaling, including association of some intrinsic pathways such as TGF-β signaling and TP53, are the crucial factors to alter TLR4 functions against breast cancer.

Keywords

Breast cancer TLR4 Metastasis 

Notes

Funding

This study was funded by Rafsanjan University of Medical Sciences.

Compliance with ethical standards

Conflict of interest

Authors have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants performed by any of the authors.

References

  1. 1.
    Rojas K, Stuckey A. Breast cancer epidemiology and risk factors. Clin Obstet Gynecol. 2016;59:651–72.CrossRefGoogle Scholar
  2. 2.
    Gu G, Dustin D, Fuqua SA. Targeted therapy for breast cancer and molecular mechanisms of resistance to treatment. Curr Opin Pharmacol. 2016;31:97–103.CrossRefGoogle Scholar
  3. 3.
    Khvalevsky E, Rivkin L, Rachmilewitz J, Galun E, Giladi H. TLR3 signaling in a hepatoma cell line is skewed towards apoptosis. J Cell Biochem. 2007;100:1301–12.CrossRefGoogle Scholar
  4. 4.
    Bagheri V, Askari A, Arababadi MK, Kennedy D. Can toll-like receptor (TLR) 2 be considered as a new target for immunotherapy against hepatitis B infection? Hum Immunol. 2014;75:549–54.CrossRefGoogle Scholar
  5. 5.
    Karimi-Googheri M, Arababadi MK. TLR3 plays significant roles against hepatitis B virus. Mol Biol Rep. 2014;41:3279–86.CrossRefGoogle Scholar
  6. 6.
    Imani Fooladi AA, Mousavi SF, Seghatoleslami S, Yazdani S, Nourani MR. Toll-like receptors: role of inflammation and commensal bacteria. Inflamm Allergy Drug Targets. 2011;10:198–207.CrossRefGoogle Scholar
  7. 7.
    Sepehri Z, Kiani Z, Kohan F, Alavian SM, Ghavami S. Toll like receptor 4 and hepatocellular carcinoma; A systematic review. Life Sci. 2017;179:80–7.CrossRefGoogle Scholar
  8. 8.
    Nguyen-Pham TN, Lim MS, Nguyen TA, Lee YK, Jin CJ, Lee HJ, et al. Type I and II interferons enhance dendritic cell maturation and migration capacity by regulating CD38 and CD74 that have synergistic effects with TLR agonists. Cell Mol Immunol. 2011;8:341–7.CrossRefGoogle Scholar
  9. 9.
    Hirayama T, Tamaki Y, Takakubo Y, Iwazaki K, Sasaki K, Ogino T, et al. Toll-like receptors and their adaptors are regulated in macrophages after phagocytosis of lipopolysaccharide-coated titanium particles. J Orthop Res. 2011;29:984–92.CrossRefGoogle Scholar
  10. 10.
    Bae YS, Lee JH, Choi SH, Kim S, Almazan F, Witztum JL, et al. Macrophages generate reactive oxygen species in response to minimally oxidized low-density lipoprotein: toll-like receptor 4- and spleen tyrosine kinase-dependent activation of NADPH oxidase 2. Circ Res. 2009;104:210–8 (21p following 8).CrossRefGoogle Scholar
  11. 11.
    Wang X, Yu X, Wang Q, Lu Y, Chen H. Expression and clinical significance of SATB1 and TLR4 in breast cancer. Oncol Lett. 2017;14:3611–5.CrossRefGoogle Scholar
  12. 12.
    Lu Y-C, Yeh W-C, Ohashi PS. LPS/TLR4 signal transduction pathway. Cytokine. 2008;42:145–51.CrossRefGoogle Scholar
  13. 13.
    Yamamoto M, Sato S, Hemmi H, Hoshino K, Kaisho T, Sanjo H, et al. Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway. Science. 2003;301:640–3.CrossRefGoogle Scholar
  14. 14.
    Qureshi ST, Larivière L, Leveque G, Clermont S, Moore KJ, Gros P, et al. Endotoxin-tolerant mice have mutations in Toll-like receptor 4 (Tlr4). J Exp Med. 1999;189:615–25.CrossRefGoogle Scholar
  15. 15.
    Zare-Bidaki M, Hakimi H, Abdollahi SH, Zainodini N, Kazemi Arababadi M, Kennedy D. TLR4 in Toxoplasmosis; friends or foe? Microb Pathog. 2014;69-70C:28–32.CrossRefGoogle Scholar
  16. 16.
    Kagan JC, Medzhitov R. Phosphoinositide-mediated adaptor recruitment controls Toll-like receptor signaling. Cell. 2006;125:943–55.CrossRefGoogle Scholar
  17. 17.
    Cario E, Gerken G, Podolsky D. Toll-like receptor 2 controls mucosal inflammation by regulating epithelial barrier function. Gastroenterology. 2007;132:1359–74.CrossRefGoogle Scholar
  18. 18.
    Fitzgerald KA, Rowe DC, Barnes BJ, Caffrey DR, Visintin A, Latz E, et al. LPS-TLR4 signaling to IRF-3/7 and NF-κB involves the Toll adapters TRAM and TRIF. J Exp Med. 2003;198:1043–55.CrossRefGoogle Scholar
  19. 19.
    Kawai T, Akira S. Toll-like receptors and their crosstalk with other innate receptors in infection and immunity. Immunity. 2011;34:637–50.CrossRefGoogle Scholar
  20. 20.
    Erridge C. Endogenous ligands of TLR2 and TLR4: agonists or assistants? J Leukoc Biol. 2010;87:989–99.CrossRefGoogle Scholar
  21. 21.
    Hortobagyi GN, de la Garza Salazar J, Pritchard K, Amadori D, Haidinger R, Hudis CA, et al. The global breast cancer burden: variations in epidemiology and survival. Clin Breast Cancer. 2005;6:391–401.CrossRefGoogle Scholar
  22. 22.
    Ginsburg O, Bray F, Coleman MP, Vanderpuye V, Eniu A, Kotha SR, et al. The global burden of women’s cancers: a grand challenge in global health. Lancet. 2017;389:847–60.CrossRefGoogle Scholar
  23. 23.
    Jazayeri SB, Saadat S, Ramezani R, Kaviani A. Incidence of primary breast cancer in Iran: Ten-year national cancer registry data report. Cancer Epidemiol. 2015;39:519–27.CrossRefGoogle Scholar
  24. 24.
    Lee J, Choi J, Chung S, Park J, Kim JE, Sung H, et al. Genetic predisposition of polymorphisms in HMGB1-related genes to breast cancer prognosis in Korean women. J Breast Cancer. 2017;20:27–34.CrossRefGoogle Scholar
  25. 25.
    Giuliano AE, Connolly JL, Edge SB, Mittendorf EA, Rugo HS, Solin LJ, et al. Breast cancer-major changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J Clin. 2017;67:290–303.CrossRefGoogle Scholar
  26. 26.
    Gil Del Alcazar CR, Huh SJ, Ekram MB, Trinh A, Liu LL, Beca F, et al. Immune escape in breast cancer during in situ to invasive carcinoma transition. Cancer Discov. 2017;7:1098–115.CrossRefGoogle Scholar
  27. 27.
    Bhatt J, Desai A, Dave J, Juneja I, Meghani H, Shah M. Clinical study of CA breast & its surgical management. Int J Res Med. 2017;6:16–22.Google Scholar
  28. 28.
    Park GS, Kim JH. Up-Regulates LPS. ICAM-1 expression in breast cancer cells by stimulating a MyD88-BLT2-ERK-linked cascade, which promotes adhesion to monocytes. Mol Cells. 2015;38:821–8.CrossRefGoogle Scholar
  29. 29.
    Ghochikyan A, Pichugin A, Bagaev A, Davtyan A, Hovakimyan A, Tukhvatulin A, et al. Targeting TLR-4 with a novel pharmaceutical grade plant derived agonist, Immunomax(R), as a therapeutic strategy for metastatic breast cancer. J Transl Med. 2014;12:322.CrossRefGoogle Scholar
  30. 30.
    Ahmed A, Wang JH, Redmond HP. Silencing of TLR4 increases tumor progression and lung metastasis in a murine model of breast cancer. Ann Surg Oncol. 2013;20(Suppl 3):389-96.Google Scholar
  31. 31.
    Vacchelli E, Galluzzi L, Rousseau V, Rigoni A, Tesniere A, Delahaye N, et al. Loss-of-function alleles of P2RX7 and TLR4 fail to affect the response to chemotherapy in non-small cell lung cancer. Oncoimmunology. 2012;1:271–8.CrossRefGoogle Scholar
  32. 32.
    Apetoh L, Tesniere A, Ghiringhelli F, Kroemer G, Zitvogel L. Molecular interactions between dying tumor cells and the innate immune system determine the efficacy of conventional anticancer therapies. Cancer Res. 2008;68:4026–30.CrossRefGoogle Scholar
  33. 33.
    Apetoh L, Ghiringhelli F, Tesniere A, Criollo A, Ortiz C, Lidereau R, et al. The interaction between HMGB1 and TLR4 dictates the outcome of anticancer chemotherapy and radiotherapy. Immunol Rev. 2007;220:47–59.CrossRefGoogle Scholar
  34. 34.
    Apetoh L, Ghiringhelli F, Tesniere A, Obeid M, Ortiz C, Criollo A, et al. Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy. Nat Med. 2007;13:1050–9.CrossRefGoogle Scholar
  35. 35.
    Bergenfelz C, Medrek C, Ekstrom E, Jirstrom K, Janols H, Wullt M, et al. Wnt5a induces a tolerogenic phenotype of macrophages in sepsis and breast cancer patients. J Immunol. 2012;188:5448–58.CrossRefGoogle Scholar
  36. 36.
    Lapteva N, Aldrich M, Rollins L, Ren W, Goltsova T, Chen SY, et al. Attraction and activation of dendritic cells at the site of tumor elicits potent antitumor immunity. Mol Ther. 2009;17:1626–36.CrossRefGoogle Scholar
  37. 37.
    Lamrani M, Sassi N, Paul C, Yousfi N, Boucher JL, Gauthier N, et al. TLR4/IFNgamma pathways induce tumor regression via NOS II-dependent NO and ROS production in murine breast cancer models. Oncoimmunology. 2016;5:e1123369.CrossRefGoogle Scholar
  38. 38.
    Zare-Bidaki M, Tsukiyama-Kohara K, Arababadi MK. Toll-like receptor 4 and hepatitis B infection: molecular mechanisms and pathogenesis. Viral Immunol. 2014;27:321–6.CrossRefGoogle Scholar
  39. 39.
    Song Y, Shi Y, Ao LH, Harken AH, Meng XZ. TLR4 mediates LPS-induced HO-1 expression in mouse liver: role of TNF-alpha and IL-1beta. World J Gastroenterol. 2003;9:1799–803.CrossRefGoogle Scholar
  40. 40.
    Hsu RY, Chan CH, Spicer JD, Rousseau MC, Giannias B, Rousseau S, et al. LPS-induced TLR4 signaling in human colorectal cancer cells increases beta1 integrin-mediated cell adhesion and liver metastasis. Cancer Res. 2011;71:1989–98.CrossRefGoogle Scholar
  41. 41.
    Chen Y, Wermeling F, Sundqvist J, Jonsson AB, Tryggvason K, Pikkarainen T, et al. A regulatory role for macrophage class A scavenger receptors in TLR4-mediated LPS responses. Eur J Immunol. 2010;40:1451–60.CrossRefGoogle Scholar
  42. 42.
    Rittirsch D, Flierl MA, Day DE, Nadeau BA, Zetoune FS, Sarma JV, et al. Cross-talk between TLR4 and FcgammaReceptorIII (CD16) pathways. PLoS Pathog. 2009;5:e1000464.CrossRefGoogle Scholar
  43. 43.
    Volk-Draper LD, Hall KL, Wilber AC, Ran S. Lymphatic endothelial progenitors originate from plastic myeloid cells activated by toll-like receptor-4. PLoS One. 2017;12:e0179257.CrossRefGoogle Scholar
  44. 44.
    Chen X, Zhao F, Zhang H, Zhu Y, Wu K, Tan G. Significance of TLR4/MyD88 expression in breast cancer. Int J Clin Exp Pathol. 2015;8:7034–9.Google Scholar
  45. 45.
    Yang H, Wang B, Wang T, Xu L, He C, Wen H, et al. Toll-like receptor 4 prompts human breast cancer cells invasiveness via lipopolysaccharide stimulation and is overexpressed in patients with lymph node metastasis. PLoS One. 2014;9:e109980.CrossRefGoogle Scholar
  46. 46.
    Green TL, Santos MF, Ejaeidi AA, Craft BS, Lewis RE, Cruse JM. Toll-like receptor (TLR) expression of immune system cells from metastatic breast cancer patients with circulating tumor cells. Exp Mol Pathol. 2014;97:44–8.CrossRefGoogle Scholar
  47. 47.
    Chalmers SA, Eidelman AS, Ewer JC, Ricca JM, Serrano A, Tucker KC, et al. A role for HMGB1, HSP60 and Myd88 in growth of murine mammary carcinoma in vitro. Cell Immunol. 2013;282:136–45.CrossRefGoogle Scholar
  48. 48.
    Ehsan N, Murad S, Ashiq T, Mansoor MU, Gul S, Khalid S, et al. Significant correlation of TLR4 expression with the clinicopathological features of invasive ductal carcinoma of the breast. Tumour Biol. 2013;34:1053–9.CrossRefGoogle Scholar
  49. 49.
    Gonzalez-Reyes S, Marin L, Gonzalez L, Gonzalez LO, del Casar JM, Lamelas ML, et al. Study of TLR3, TLR4 and TLR9 in breast carcinomas and their association with metastasis. BMC Cancer. 2010;10:665.CrossRefGoogle Scholar
  50. 50.
    Yang H, Zhou H, Feng P, Zhou X, Wen H, Xie X, et al. Reduced expression of Toll-like receptor 4 inhibits human breast cancer cells proliferation and inflammatory cytokines secretion. J Exp Clin Cancer Res. 2010;29:92.CrossRefGoogle Scholar
  51. 51.
    Ma FJ, Liu ZB, Hu X, Ling H, Li S, Wu J, et al. Prognostic value of myeloid differentiation primary response 88 and Toll-like receptor 4 in breast cancer patients. PLoS One. 2014;9:e111639.CrossRefGoogle Scholar
  52. 52.
    Volk-Draper L, Hall K, Griggs C, Rajput S, Kohio P, DeNardo D, et al. Paclitaxel therapy promotes breast cancer metastasis in a TLR4-dependent manner. Cancer Res. 2014;74:5421–34.CrossRefGoogle Scholar
  53. 53.
    Rajput S, Volk-Draper LD, Ran S. TLR4 is a novel determinant of the response to paclitaxel in breast cancer. Mol Cancer Ther. 2013;12:1676–87.CrossRefGoogle Scholar
  54. 54.
    Mehmeti M, Allaoui R, Bergenfelz C, Saal LH, Ethier SP, Johansson ME, et al. Expression of functional toll like receptor 4 in estrogen receptor/progesterone receptor-negative breast cancer. Breast Cancer Res. 2015;17:130.CrossRefGoogle Scholar
  55. 55.
    Vacchelli E, Enot DP, Pietrocola F, Zitvogel L, Kroemer G. Impact of pattern recognition receptors on the prognosis of breast cancer patients undergoing adjuvant chemotherapy. Cancer Res. 2016;76:3122–6.CrossRefGoogle Scholar
  56. 56.
    Wang CH, Wang PJ, Hsieh YC, Lo S, Lee YC, Chen YC, et al. Resistin facilitates breast cancer progression via TLR4-mediated induction of mesenchymal phenotypes and stemness properties. Oncogene. 2017;9:357.Google Scholar
  57. 57.
    Chang H, Wang Y, Yin X, Liu X, Xuan H. Ethanol extract of propolis and its constituent caffeic acid phenethyl ester inhibit breast cancer cells proliferation in inflammatory microenvironment by inhibiting TLR4 signal pathway and inducing apoptosis and autophagy. BMC Complement Altern Med. 2017;17:471.CrossRefGoogle Scholar
  58. 58.
    Edwardson DW, Boudreau J, Mapletoft J, Lanner C, Kovala AT, Parissenti AM. Inflammatory cytokine production in tumor cells upon chemotherapy drug exposure or upon selection for drug resistance. PLoS One. 2017;12:e0183662.CrossRefGoogle Scholar
  59. 59.
    Erez N, Glanz S, Raz Y, Avivi C, Barshack I. Cancer associated fibroblasts express pro-inflammatory factors in human breast and ovarian tumors. Biochem Biophys Res Commun. 2013;437:397–402.CrossRefGoogle Scholar
  60. 60.
    Wang M, Zhang J, Huang Y, Ji S, Shao G, Feng S, et al. Cancer-associated fibroblasts autophagy enhances progression of triple-negative breast cancer cells. Med Sci Monit. 2017;23:3904–12.CrossRefGoogle Scholar
  61. 61.
    Zhao XL, Lin Y, Jiang J, Tang Z, Yang S, Lu L, et al. High-mobility group box 1 released by autophagic cancer-associated fibroblasts maintains the stemness of luminal breast cancer cells. J Pathol. 2017;243:376–89.CrossRefGoogle Scholar
  62. 62.
    Han L, Liu B, Jiang L, Liu J, Han S. MicroRNA-497 downregulation contributes to cell proliferation, migration, and invasion of estrogen receptor alpha negative breast cancer by targeting estrogen-related receptor alpha. Tumour Biol. 2016;37:13205–14.CrossRefGoogle Scholar
  63. 63.
    Xu M, Wang HF, Zhang YY, Zhuang HW. Protection of rats spinal cord ischemia-reperfusion injury by inhibition of MiR-497 on inflammation and apoptosis: possible role in pediatrics. Biomed Pharmacother. 2016;81:337–44.CrossRefGoogle Scholar
  64. 64.
    Ibrahim SA, Yip GW, Stock C, Pan JW, Neubauer C, Poeter M, et al. Targeting of syndecan-1 by microRNA miR-10b promotes breast cancer cell motility and invasiveness via a Rho-GTPase- and E-cadherin-dependent mechanism. Int J Cancer. 2012;131:E884-96.CrossRefGoogle Scholar
  65. 65.
    Tosun S, Fried S, Niggemann B, Zanker KS, Dittmar T. Hybrid cells derived from human breast cancer cells and human breast epithelial cells exhibit differential TLR4 and TLR9 signaling. Int J Mol Sci. 2016;17:726.CrossRefGoogle Scholar
  66. 66.
    Fried S, Tosun S, Troost G, Keil S, Zaenker KS, Dittmar T. Lipopolysaccharide (LPS) promotes apoptosis in human breast epithelial × breast cancer hybrids, but not in parental cells. PLoS One. 2016;11:e0148438.CrossRefGoogle Scholar
  67. 67.
    Richard V, Kindt N, Saussez S. Macrophage migration inhibitory factor involvement in breast cancer (Review). Int J Oncol. 2015;47:1627–33.CrossRefGoogle Scholar
  68. 68.
    Lv W, Chen N, Lin Y, Ma H, Ruan Y, Li Z, et al. Macrophage migration inhibitory factor promotes breast cancer metastasis via activation of HMGB1/TLR4/NF kappa B axis. Cancer Lett. 2016;375:245–55.CrossRefGoogle Scholar
  69. 69.
    Bergenfelz C, Gaber A, Allaoui R, Mehmeti M, Jirstrom K, Leanderson T, et al. S100A9 expressed in ER(-)PgR(-) breast cancers induces inflammatory cytokines and is associated with an impaired overall survival. Br J Cancer. 2015;113:1234–43.CrossRefGoogle Scholar
  70. 70.
    Arai K, Takano S, Teratani T, Ito Y, Yamada T, Nozawa R. S100A8 and S100A9 overexpression is associated with poor pathological parameters in invasive ductal carcinoma of the breast. Curr Cancer Drug Targets. 2008;8:243–52.CrossRefGoogle Scholar
  71. 71.
    Xu F, Wang F, Yang T, Sheng Y, Zhong T, Chen Y. Differential drug resistance acquisition to doxorubicin and paclitaxel in breast cancer cells. Cancer Cell Int. 2014;14:142.Google Scholar
  72. 72.
    Howe LR, Subbaramaiah K, Hudis CA, Dannenberg AJ. Molecular pathways: adipose inflammation as a mediator of obesity-associated cancer. Clin Cancer Res. 2013;19:6074–83.CrossRefGoogle Scholar
  73. 73.
    Zhou YH, Liao SJ, Li D, Luo J, Wei JJ, Yan B, et al. TLR4 ligand/H(2)O(2) enhances TGF-beta1 signaling to induce metastatic potential of non-invasive breast cancer cells by activating non-Smad pathways. PLoS One. 2013;8:e65906.CrossRefGoogle Scholar
  74. 74.
    Li J, Yin J, Shen W, Gao R, Liu Y, Chen Y, et al. TLR4 promotes breast cancer metastasis via Akt/GSK3beta/beta-catenin pathway upon LPS stimulation. Anat Rec (Hoboken). 2017;300:1219–29.CrossRefGoogle Scholar
  75. 75.
    Egunsola AT, Zawislak CL, Akuffo AA, Chalmers SA, Ewer JC, Vail CM, et al. Growth, metastasis, and expression of CCL2 and CCL5 by murine mammary carcinomas are dependent upon Myd88. Cell Immunol. 2012;272:220–9.CrossRefGoogle Scholar
  76. 76.
    Liao SJ, Zhou YH, Yuan Y, Li D, Wu FH, Wang Q, et al. Triggering of Toll-like receptor 4 on metastatic breast cancer cells promotes alphavbeta3-mediated adhesion and invasive migration. Breast Cancer Res Treat. 2012;133:853–63.CrossRefGoogle Scholar
  77. 77.
    Petricevic B, Vrbanec D, Jakic-Razumovic J, Brcic I, Rabic D, Badovinac T, et al. Expression of Toll-like receptor 4 and beta 1 integrin in breast cancer. Med Oncol. 2012;29:486–94.CrossRefGoogle Scholar
  78. 78.
    Haricharan S, Brown P. TLR4 has a TP53-dependent dual role in regulating breast cancer cell growth. Proc Natl Acad Sci USA. 2015;112:E3216-25.CrossRefGoogle Scholar
  79. 79.
    Oliveira TF, Maues T, Ramundo MS, Figueiredo AMS, de Mello MFV, El-Jaick KB, et al. TP53 gene expression levels and tumor aggressiveness in canine mammary carcinomas. J Vet Diagn Invest. 2017;29:865–8.CrossRefGoogle Scholar
  80. 80.
    Morikawa T, Kuchiba A, Liao X, Imamura Y, Yamauchi M, Qian ZR, et al. Tumor TP53 expression status, body mass index and prognosis in colorectal cancer. Int J Cancer. 2012;131:1169–78.CrossRefGoogle Scholar
  81. 81.
    Pakos EE, Kyzas PA, Ioannidis JP. Prognostic significance of TP53 tumor suppressor gene expression and mutations in human osteosarcoma: a meta-analysis. Clin Cancer Res. 2004;10:6208–14.CrossRefGoogle Scholar
  82. 82.
    Slattery ML, Lundgreen A, Torres-Mejia G, Wolff RK, Hines L, Baumgartner K, et al. Diet and lifestyle factors modify immune/inflammation response genes to alter breast cancer risk and prognosis: the Breast Cancer Health Disparities Study. Mutat Res. 2014;770:19–28.CrossRefGoogle Scholar
  83. 83.
    Zhu L, Yuan H, Jiang T, Wang R, Ma H, Zhang S. Association of TLR2 and TLR4 polymorphisms with risk of cancer: a meta-analysis. PLoS One. 2013;8:e82858.CrossRefGoogle Scholar
  84. 84.
    Yang CX, Li CY, Feng W. Toll-like receptor 4 genetic variants and prognosis of breast cancer. Tissue Antigens. 2013;81:221–6.CrossRefGoogle Scholar
  85. 85.
    Theodoropoulos GE, Saridakis V, Karantanos T, Michalopoulos NV, Zagouri F, Kontogianni P, et al. Toll-like receptors gene polymorphisms may confer increased susceptibility to breast cancer development. Breast. 2012;21:534–8.CrossRefGoogle Scholar
  86. 86.
    Semlali A, Jalouli M, Parine NR, Al Amri A, Arafah M, Al Naeem A, et al. Toll-like receptor 4 as a predictor of clinical outcomes of estrogen receptor-negative breast cancer in Saudi women. Onco Targets Ther. 2017;10:1207–16.CrossRefGoogle Scholar

Copyright information

© The Japanese Breast Cancer Society 2018

Authors and Affiliations

  • Morteza Khademalhosseini
    • 1
    • 2
  • Mohammad Kazemi Arababadi
    • 2
    • 3
    Email author
  1. 1.Geriatric Care Research CenterRafsanjan University of Medical SciencesRafsanjanIran
  2. 2.Department of Laboratory Sciences, Faculty of ParamedicineRafsanjan University of Medical SciencesRafsanjanIran
  3. 3.Immunology of Infectious Diseases Research Center, Research Institute of Basic Medical SciencesRafsanjan University of Medical SciencesRafsanjanIran

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