Login Register Cart 0
Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

The Therapeutic Potential of Targeting the Toll-like Receptor Pathway in Breast Cancer

Author(s): Younes Toroghian, Reza Khayyami, Seyed Mahdi Hassanian, Mohammadreza Nassiri, Gordon A. Ferns, Majid Khazaei* and Amir Avan*

Volume 28, Issue 27, 2022

Published on: 12 August, 2022

Page: [2203 - 2210] Pages: 8

DOI: 10.2174/1381612828666220728154012

Price: $65

Abstract

The toll-like receptor (TLR) signaling pathway plays a key role in inducing immune responses and is shown to be expressed in immune cells and tumor cells and is involved in the progression of several malignancies, including breast cancer. These findings provide proof of the concept of targeting this pathway as a potential therapeutic option in the treatment of breast cancer. Moreover, there is a growing body of data showing the activation of TLRs in the tumor microenvironment and its dual function as anti-tumoral (dendritic T and natural killer cells activation) or pro-tumoral activity (cell proliferation, and drug resistance). Several agents have been developed for targeting this pathway, and one of these inhibitors, called Bacillus Calmette-Guerin (an agonist of TLR2 and TLR4), is recently being approved by FDA for immunotherapy of bladder cancer. This review summarizes the current knowledge of the mechanisms of action of TLR pathways in the development/progression of cancer for better management of this disease.

Keywords: Toll-like receptors, breast cancer progression, cell proliferation, drug resistance, tumor cells, Bacillus Calmette-Guerin.

Next »
[1]
Bhatelia K, Singh K, Singh R. TLRs: Linking inflammation and breast cancer. Cell Signal 2014; 26(11): 2350-7.
[http://dx.doi.org/10.1016/j.cellsig.2014.07.035] [PMID: 25093807]
[2]
Kidd LC, Rogers EN, Yeyeodu ST, Jones DZ, Kimbro KS. Contribution of toll-like receptor signaling pathways to breast tumorigenesis and treatment. Breast Cancer 2013; 5: 43-51.
[http://dx.doi.org/10.2147/BCTT.S29172] [PMID: 24648757]
[3]
Yusuf N. Toll-like receptor mediated regulation of breast cancer: A case of mixed blessings. Front Immunol 2014; 5(224): 224.
[PMID: 24904578]
[4]
Mehmeti M, Allaoui R, Bergenfelz C, et al. Expression of functional toll like receptor 4 in estrogen receptor/progesterone receptor-negative breast cancer. Breast Cancer Res 2015; 17(1): 130.
[http://dx.doi.org/10.1186/s13058-015-0640-x] [PMID: 26392082]
[5]
Shuang C, Weiguang Y, Zhenkun F, et al. Toll-like receptor 5 gene polymorphism is associated with breast cancer susceptibility. Oncotarget 2017; 8(51): 88622-9.
[http://dx.doi.org/10.18632/oncotarget.20242] [PMID: 29179462]
[6]
Moradi-Marjaneh R, Hassanian SM, Hasanzadeh M, et al. Therapeutic potential of toll-like receptors in treatment of gynecological cancers. IUBMB Life 2019; 71(5): 549-64.
[http://dx.doi.org/10.1002/iub.2011] [PMID: 30729633]
[7]
Zhao S, Zhang Y, Zhang Q, Wang F, Zhang D. Toll-like receptors and prostate cancer. Front Immunol 2014; 5(352): 352.
[PMID: 25101092]
[8]
Ahmed A, Redmond HP, Wang JH. Links between Toll-like receptor 4 and breast cancer. OncoImmunology 2013; 2(2)e22945
[http://dx.doi.org/10.4161/onci.22945] [PMID: 23526132]
[9]
Kutikhin AG. Association of polymorphisms in TLR genes and in genes of the Toll-like receptor signaling pathway with cancer risk. Hum Immunol 2011; 72(11): 1095-116.
[http://dx.doi.org/10.1016/j.humimm.2011.07.307] [PMID: 21872627]
[10]
Moradi-Marjaneh R, Hassanian SM, Fiuji H, et al. Toll like receptor signaling pathway as a potential therapeutic target in colorectal cancer. J Cell Physiol 2018; 233(8): 5613-22.
[http://dx.doi.org/10.1002/jcp.26273] [PMID: 29150944]
[11]
Chen R, Alvero AB, Silasi DA, Mor G. Inflammation, cancer and chemoresistance: Taking advantage of the toll-like receptor signaling pathway. Am J Reprod Immunol 2007; 57(2): 93-107.
[http://dx.doi.org/10.1111/j.1600-0897.2006.00441.x] [PMID: 17217363]
[12]
Xie W, Wang Y, Huang Y, Yang H, Wang J, Hu Z. Toll-like receptor 2 mediates invasion via activating NF-kappaB in MDAMB- 231 breast cancer cells. Biochem Biophys Res Commun 2009; 379(4): 1027-32.
[http://dx.doi.org/10.1016/j.bbrc.2009.01.009] [PMID: 19141294]
[13]
Xie W, Huang Y, Xie W, Guo A, Wu W. Bacteria peptidoglycan promoted breast cancer cell invasiveness and adhesiveness by targeting Toll-like receptor 2 in the cancer cells. PLoS One 2010; 5(5)e10850
[http://dx.doi.org/10.1371/journal.pone.0010850] [PMID: 20520770]
[14]
Verovkina N, Sivak LA, Lyalkin S, Rossokcha ZI, Fedorovna PE. 226PThe correlation between Toll-like receptor genes polymorphisms, tumor microenvironment characteristics and the effectiveness of preoperative chemotherapy for locally advanced breast cancer. Annals Oncol 2017; 28(suppl_5).
[15]
Chow A, Zhou W, Liu L, et al. Macrophage immunomodulation by breast cancer-derived exosomes requires Toll-like receptor 2-mediated activation of NF-κB. Sci Rep 2014; 4(1): 5750.
[http://dx.doi.org/10.1038/srep05750] [PMID: 25034888]
[16]
Venkatesh AK, Pate M, Benencia F. Abstract 1333: Upregulation of chemokines including RANTES/CCL5 upon Toll-like receptor 3 activation in breast cancer: Association with leukocyte infiltration. Cancer Res 2010; 70(8): 1333.
[17]
Obeid E, Nanda R, Li T, Zhang B, Mueller J, Olopade OI. Association of downregulation of Toll-like receptor 3 (TLR3) expression with aggressive breast cancer (BC). J Clin Oncol 2013; 31(15): 11035.
[http://dx.doi.org/10.1200/jco.2013.31.15_suppl.11035]
[18]
Alizadeh N, Amiri MM, Salek Moghadam A, et al. Effect of Toll-like receptor 3 agonists on the functionality and metastatic properties of breast cancer cell model. Iran J Allergy Asthma Immunol 2013; 12(2): 161-7.
[PMID: 23754355]
[19]
Ma FJ, Liu ZB, Hu X, et al. Prognostic value of myeloid differentiation primary response 88 and Toll-like receptor 4 in breast cancer patients. PLoS One 2014; 9(10)e111639
[http://dx.doi.org/10.1371/journal.pone.0111639] [PMID: 25360699]
[20]
Yang H, Wang B, Wang T, 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(10): e109980.
[21]
Yang H, Zhou H, Feng P, 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(1): 92.
[http://dx.doi.org/10.1186/1756-9966-29-92] [PMID: 20618976]
[22]
Semlali A, Jalouli M, Parine NR, et al. Toll-like receptor 4 as a predictor of clinical outcomes of estrogen receptor-negative breast cancer in Saudi women. OncoTargets Ther 2017; 10: 1207-16.
[http://dx.doi.org/10.2147/OTT.S112165] [PMID: 28280355]
[23]
Ahmed A, Wang JH, Redmond HP. Toll like receptor 4-a weapon for host defences and a shield for cancer cells in breast cancer. Br J Surg 2011; 98: 107.
[24]
Sootichote R, Thuwajit P, Singsuksawat E, et al. Compound A attenuates toll-like receptor 4-mediated paclitaxel resistance in breast cancer and melanoma through suppression of IL-8. BMC Cancer 2018; 18(1): 231.
[http://dx.doi.org/10.1186/s12885-018-4155-6] [PMID: 29486738]
[25]
Cai Z, Sanchez A, Shi Z, Zhang T, Liu M, Zhang D. Activation of Toll-like receptor 5 on breast cancer cells by flagellin suppresses cell proliferation and tumor growth. Cancer Res 2011; 71(7): 2466-75.
[http://dx.doi.org/10.1158/0008-5472.CAN-10-1993] [PMID: 21427357]
[26]
Vatner R, Demaria S, Fenton-Kerimian M, et al. Novel combination of Toll-like receptor (TLR)-7 agonist imiquimod and local radiation therapy in the treatment of metastatic breast cancer involving the skin or chest wall. Int J Radiat Oncol Biol Phys 2013; 87(2): S111.
[27]
Dewan MZ, Vanpouille-Box C, Kawashima N, et al. Synergy of topical Toll-like receptor 7 agonist with radiation and low-dose cyclophosphamide in a mouse model of cutaneous breast cancer. Clin Cancer Res 2012; 18(24): 6668-78.
[http://dx.doi.org/10.1158/1078-0432.CCR-12-0984] [PMID: 23048078]
[28]
Yin T, He S, Wang Y. Toll-like receptor 7/8 agonist, R848, exhibits antitumoral effects in a breast cancer model. Mol Med Rep 2015; 12(3): 3515-20.
[http://dx.doi.org/10.3892/mmr.2015.3885] [PMID: 26043701]
[29]
Obeid EI, Khramstova G, Zhang B, et al. Abstract P5-01-04: Activation of Toll-like receptor 7 (TLR7) confers protection in human breast cancer. Cancer Res 2013; 73 (24_Supplement): P5-01-04.
[30]
Shahriari S, Rezaeifard S, Moghimi HR, Khorramizadeh MR, Faghih Z. Cell membrane and intracellular expression of toll-like receptor 9 (TLR9) in colorectal cancer and breast cancer cell-lines. Cancer Biomark 2017; 18(4): 375-80.
[http://dx.doi.org/10.3233/CBM-160260] [PMID: 28106541]
[31]
Berger R, Fiegl H, Goebel G, et al. Toll-like receptor 9 expression in breast and ovarian cancer is associated with poorly differentiated tumors. Cancer Sci 2010; 101(4): 1059-66.
[http://dx.doi.org/10.1111/j.1349-7006.2010.01491.x] [PMID: 20156214]
[32]
Qiu J, Shao S, Yang G, Shen Z, Zhang Y. Association of Toll like receptor 9 expression with lymph node metastasis in human breast cancer. Neoplasma 2011; 58(3): 251-5.
[http://dx.doi.org/10.4149/neo_2011_03_251] [PMID: 21391743]
[33]
Jukkola-Vuorinen A, Rahko E, Vuopala KS, et al. Toll-like receptor-9 expression is inversely correlated with estrogen receptor status in breast cancer. J Innate Immun 2009; 1(1): 59-68.
[http://dx.doi.org/10.1159/000151602] [PMID: 20375566]
[34]
Thompson JW, Keene K, Hinton B, et al. Toll-like receptor-9 expression does not predict for breast cancer specific outcome in African-American triple-negative breast cancer patients. Int J Radiat Oncol Biol Phys 2014; 90(1): S815.
[http://dx.doi.org/10.1016/j.ijrobp.2014.05.2349]
[35]
Shi J-P, Xia T-S, Ding Q, Liu X-A, Zha X-M, Wang S. CpG oligonucleotides activating Toll-Like receptor 9 promotes invasion of breast cancer cells. Acta Universitatis Medicinalis Nanjing 2011; 8: 17.
[36]
Nava-Parada P, Herron A, Knutson KL, Pease L, Celis E. Breast cancer vaccines: Maximizing peptide-based vaccines by regulatory T cell depletion and Toll-like receptor 9 activation. BMC Cancer 2007; 7(1): A2.
[http://dx.doi.org/10.1186/1471-2407-7-S1-A2]
[37]
Graves DE. Toll-like receptor-9-mediated invasion in breast cancer. Alabama Univ In Birmingham 2011.
[http://dx.doi.org/10.21236/ADA549125]
[38]
Madheswaran S, Sumantran VN, Natarajan S. Amphotericin B abolishes the cytotoxic effect of Toll-like receptor 9 agonist CpG Oligonucleotides in breast cancer cell line MCF-7. Natl J Physiol Pharm Pharmacol 2017; 7(6): 654.
[http://dx.doi.org/10.5455/njppp.2017.7.0100322022017]
[39]
Scriven PN, Kirby TL, Ogilvie CM. FISH for pre-implantation genetic diagnosis. J Vis Exp 2011; (48): e2570
[PMID: 21403624]

Rights & Permissions Print Cite
Article Metrics
19
1
© 2024 Bentham Science Publishers | Privacy Policy