Generic placeholder image

Current Molecular Medicine

Editor-in-Chief

ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

Review Article

Heat Shock Proteins Regulating Toll-like Receptors and the Immune System could be a Novel Therapeutic Target for Melanoma

Author(s): Navid Shomali, Leila Sadat Hatamnezhad, Saeed Tarzi, Rozita Tamjidifar, Huaxi Xu* and Siamak Sandoghchian Shotorbani*

Volume 21, Issue 1, 2021

Published on: 11 May, 2020

Page: [15 - 24] Pages: 10

DOI: 10.2174/1566524020666200511091540

Price: $65

Abstract

Melanoma is a serious type of skin cancer, which develops in melanocyte cells. Although it is less common than some other skin cancers, it can be far more dangerous if not treated at an early stage because of its ability to spread rapidly to other organs. Heat shock proteins (HSP) are intracellular molecular chaperones of naive proteins, which are induced in response to stressful conditions. HSP is released into the extracellular milieu and binds to Toll-like receptors (TLRs) to regulate immune responses, such as cytokine and chemokine release. HSPs can release and bind to tumor-specific antigens, with cross-presentation of major histocompatibility complex (MHC) class I antigens. TLRs are innate immune system receptors, involved in the melanoma growth pathway through HSP activation. Melanocytes express TLR4 and TLR9 to modulate immune responses. Many TLR ligands are considered as proper adjuvant candidates, as they can activate dendritic cells. Targeting some TLRs, such as TLR7 and TLR9, is an available option for treating melanoma. In this review, we aimed to determine the relationship between TLRs and HSP groups in melanoma.

Keywords: HSPs, TLRs, Immune system, Therapeutic target, Prognostic factor, Melanoma.

[1]
Takazawa Y, Kiniwa Y, Ogawa E, et al. Toll-like receptor 4 signaling promotes the migration of human melanoma cells. Tohoku J Exp Med 2014; 234(1): 57-65.
[http://dx.doi.org/10.1620/tjem.234.57] [PMID: 25175033]
[2]
Eiró N, Ovies C, Fernandez-Garcia B, et al. Expression of TLR3, 4, 7 and 9 in cutaneous malignant melanoma: relationship with clinicopathological characteristics and prognosis. Arch Dermatol Res 2013; 305(1): 59-67.
[http://dx.doi.org/10.1007/s00403-012-1300-y] [PMID: 23179584]
[3]
Sadat-Hatamnezhad L, Tanomand A, Mahmoudi J, Sandoghchian Shotorbani S. Activation of toll-like receptors 2 by high-mobility group box 1 in monocytes from patients with ischemic stroke. Iran Biomed J 2016; 20(4): 223-8.
[PMID: 27040385]
[4]
Goto Y, Arigami T, Kitago M, et al. Activation of Toll-like receptors 2, 3, and 4 on human melanoma cells induces inflammatory factors. Mol Cancer Ther 2008; 7(11): 3642-53.
[http://dx.doi.org/10.1158/1535-7163.MCT-08-0582] [PMID: 19001446]
[5]
Iyengar NM, Gucalp A, Dannenberg AJ, Hudis CA. Obesity and cancer mechanisms: tumor microenvironment and inflammation. J Clin Oncol 2016; 34(35): 4270-6.
[http://dx.doi.org/10.1200/JCO.2016.67.4283] [PMID: 27903155]
[6]
Pivarcsi A, Nagy I, Kemeny L. Innate immunity in the skin: how keratinocytes fight against pathogens. Curr Immunol Rev 2005; 1(1): 29-42.
[http://dx.doi.org/10.2174/1573395052952941]
[7]
Corrales L, Matson V, Flood B, Spranger S, Gajewski TF. Innate immune signaling and regulation in cancer immunotherapy. Cell Res 2017; 27(1): 96-108.
[http://dx.doi.org/10.1038/cr.2016.149] [PMID: 27981969]
[8]
Li K, Qu S, Chen X, Wu Q, Shi M. Promising targets for cancer immunotherapy: TLRs, RLRs, and STING-mediated innate immune pathways. Int J Mol Sci 2017; 18(2): 404.
[http://dx.doi.org/10.3390/ijms18020404] [PMID: 28216575]
[9]
Van Vliet A, Martin S, Garg A, Agostinis P. Seminars in cancer biology. Elsevier 2015; Vol. 33: pp. 74-85.
[10]
Li X, Kanegasaki S, Jin F, et al. Simultaneous induction of HSP70 expression, and degranulation, in IgE/Ag-stimulated or extracellular HSP70-stimulated mast cells. Allergy 2018; 73(2): 361-8.
[http://dx.doi.org/10.1111/all.13296] [PMID: 28857181]
[11]
Calderwood SK, Gong J, Murshid A. Extracellular HSPs: the complicated roles of extracellular HSPs in immunity. Front Immunol 2016; 7: 159.
[http://dx.doi.org/10.3389/fimmu.2016.00159] [PMID: 27199984]
[12]
Ikwegbue PC, Masamba P, Oyinloye BE, Kappo AP. Roles of heat shock proteins in apoptosis, oxidative stress, human inflammatory diseases, and cancer. Pharmaceuticals (Basel) 2017; 11(1): 2.
[http://dx.doi.org/10.3390/ph11010002] [PMID: 29295496]
[13]
Vijay K. Toll-like receptors in immunity and inflammatory diseases: Past, present, and future. Int Immunopharmacol 2018; 59: 391-412.
[http://dx.doi.org/10.1016/j.intimp.2018.03.002] [PMID: 29730580]
[14]
Ramaswamy A, Wei P, Pan F. Heat Shock Proteins in Signaling Pathways. Springer 2019; pp. 183-215.
[http://dx.doi.org/10.1007/978-3-030-03952-3_10]
[15]
Shevtsov M, Multhoff G. Heat shock protein–peptide and HSP-based immunotherapies for the treatment of cancer. Front Immunol 2016; 7: 171.
[http://dx.doi.org/10.3389/fimmu.2016.00171] [PMID: 27199993]
[16]
Radons J. The human HSP70 family of chaperones: where do we stand? Cell Stress Chaperones 2016; 21(3): 379-404.
[http://dx.doi.org/10.1007/s12192-016-0676-6] [PMID: 26865365]
[17]
Milani V, Noessner E, Ghose S, et al. Heat shock protein 70: role in antigen presentation and immune stimulation. Int J Hyperthermia 2002; 18(6): 563-75.
[http://dx.doi.org/10.1080/02656730210166140] [PMID: 12537755]
[18]
Moldogazieva NT, Lutsenko SV, Terentiev AA. Reactive Oxygen and Nitrogen Species-Induced Protein Modifications: Implication in Carcinogenesis and Anticancer Therapy. Cancer Res 2018; 78(21): 6040-7.
[http://dx.doi.org/10.1158/0008-5472.CAN-18-0980] [PMID: 30327380]
[19]
Kumada K, Fuse N, Tamura T, Okamori C, Kurata S. HSP70/DNAJA3 chaperone/cochaperone regulates NF-κB activity in immune responses. Biochem Biophys Res Commun 2019; 513(4): 947-51.
[http://dx.doi.org/10.1016/j.bbrc.2019.04.077] [PMID: 31005254]
[20]
Deane C. Localization of Heat Shock Proteins HSPA6 (Hsp70B′) HSPA1A (Hsp70-1) and HSPA8 (Hsc70) in Cultured Human Neuronal Cells. 2019.
[21]
Geng J, Li H, Huang C, et al. Functional analysis of HSPA1A and HSPA8 in parturition. Biochem Biophys Res Commun 2017; 483(1): 371-9.
[http://dx.doi.org/10.1016/j.bbrc.2016.12.136] [PMID: 28025138]
[22]
Wang H, Pezeshki AM, Yu X, Guo C, Subjeck JR, Wang XY. The endoplasmic reticulum chaperone GRP170: from immunobiology to cancer therapeutics. Front Oncol 2015; 4: 377.
[http://dx.doi.org/10.3389/fonc.2014.00377] [PMID: 25629003]
[23]
Berthenet K. La protéine HSP110: rôle dans le développement tumoral et sur l'immunogénicité du cancer colorectal 2015.
[24]
He J, Wang H. HspA1B Is a Prognostic Biomarker and Correlated With Immune Infiltrates in different subtypes of Breast Cancers. bioRxiv 2019.725861.
[25]
Akhter S, Chakraborty S, Moutinho D, et al. The human VGF-derived bioactive peptide TLQP-21 binds heat shock 71 kDa protein 8 (HSPA8)on the surface of SH-SY5Y cells. PLoS One 2017; 12(9)e0185176
[http://dx.doi.org/10.1371/journal.pone.0185176] [PMID: 28934328]
[26]
Quek D, Nguyen L, Fan H, Silver D. Archive for the ‘Neuroscience’Category. J Biol Chem 2016.
[27]
Jagadish N, Agarwal S, Gupta N, et al. Heat shock protein 70-2 (HSP70-2) overexpression in breast cancer. J Exp Clin Cancer Res 2016; 35(1): 150.
[http://dx.doi.org/10.1186/s13046-016-0425-9] [PMID: 27658496]
[28]
Vabulas RM, Ahmad-Nejad P, Ghose S, Kirschning CJ, Issels RD, Wagner H. HSP70 as endogenous stimulus of the Toll/interleukin-1 receptor signal pathway. J Biol Chem 2002; 277(17): 15107-12.
[http://dx.doi.org/10.1074/jbc.M111204200] [PMID: 11842086]
[29]
Toomey D, Conroy H, Jarnicki AG, Higgins SC, Sutton C, Mills KH. Therapeutic vaccination with dendritic cells pulsed with tumor-derived Hsp70 and a COX-2 inhibitor induces protective immunity against B16 melanoma. Vaccine 2008; 26(27-28): 3540-9.
[http://dx.doi.org/10.1016/j.vaccine.2008.04.005] [PMID: 18479787]
[30]
Kottke T, Sanchez-Perez L, Diaz RM, et al. Induction of hsp70-mediated Th17 autoimmunity can be exploited as immunotherapy for metastatic prostate cancer. Cancer Res 2007; 67(24): 11970-9.
[http://dx.doi.org/10.1158/0008-5472.CAN-07-2259] [PMID: 18089828]
[31]
Sanchez-Perez L, Kottke T, Daniels GA, et al. Killing of normal melanocytes, combined with heat shock protein 70 and CD40L expression, cures large established melanomas. J Immunol 2006; 177(6): 4168-77.
[http://dx.doi.org/10.4049/jimmunol.177.6.4168] [PMID: 16951382]
[32]
Pulido J, Kottke T, Thompson J, et al. Using virally expressed melanoma cDNA libraries to identify tumor-associated antigens that cure melanoma. Nat Biotechnol 2012; 30(4): 337-43.
[http://dx.doi.org/10.1038/nbt.2157] [PMID: 22426030]
[33]
Fang H, Wu Y, Huang X, et al. Toll-like receptor 4 (TLR4) is essential for Hsp70-like protein 1 (HSP70L1) to activate dendritic cells and induce Th1 response. J Biol Chem 2011; 286(35): 30393-400.
[http://dx.doi.org/10.1074/jbc.M111.266528] [PMID: 21730052]
[34]
Gong W, Wang Z-Y, Chen G-X, Liu YQ, Gu XY, Liu WW. Invasion potential of H22 hepatocarcinoma cells is increased by HMGB1-induced tumor NF-κB signaling via initiation of HSP70. Oncol Rep 2013; 30(3): 1249-56.
[http://dx.doi.org/10.3892/or.2013.2595] [PMID: 23836405]
[35]
Testori A, Richards J, Whitman E, et al. Phase III comparison of vitespen, an autologous tumor-derived heat shock protein gp96 peptide complex vaccine, with physician’s choice of treatment for stage IV melanoma: the C-100-21 Study Group. Clin Oncol 2006.
[36]
Wood C, Srivastava P, Bukowski R, et al. C-100-12 RCC Study Group. An adjuvant autologous therapeutic vaccine (HSPPC-96; vitespen) versus observation alone for patients at high risk of recurrence after nephrectomy for renal cell carcinoma: a multicentre, open-label, randomised phase III trial. Lancet 2008; 372(9633): 145-54.
[http://dx.doi.org/10.1016/S0140-6736(08)60697-2] [PMID: 18602688]
[37]
Kwon S-M, Kim S, Song N-J, et al. Antiadipogenic and proosteogenic effects of luteolin, a major dietary flavone, are mediated by the induction of DnaJ (Hsp40) Homolog, Subfamily B, Member 1. J Nutr Biochem 2016; 30: 24-32.
[http://dx.doi.org/10.1016/j.jnutbio.2015.11.013] [PMID: 27012618]
[38]
Mitsugi R, Itoh T, Fujiwara R. Expression of human DNAJ (Heat Shock Protein-40) B3 in humanized UDP-glucuronosyltransferase 1 mice. Int J Mol Sci 2015; 16(7): 14997-5008.
[http://dx.doi.org/10.3390/ijms160714997] [PMID: 26147428]
[39]
Weisbart RH, Nishimura RN, Hansen JE. Google Patents 2018.
[40]
Ambarus CA, Yeremenko N, Baeten DL. Altered cytokine expression by macrophages from HLA-B27-positive spondyloarthritis patients without evidence of endoplasmic reticulum stress. Rheumatol Adv Pract 2018; 2(1): rky014...
[41]
Kastenhuber ER, Lalazar G, Houlihan SL, et al. DNAJB1-PRKACA fusion kinase interacts with β-catenin and the liver regenerative response to drive fibrolamellar hepatocellular carcinoma. Proc Natl Acad Sci USA 2017; 114(50): 13076-84.
[http://dx.doi.org/10.1073/pnas.1716483114] [PMID: 29162699]
[42]
Karki A, Putra J, LaQuaglia M, Perez-Atayde A, Vakili K. AACR 2018.
[43]
Lu T-W, Zhang P, Cianfrocco M, et al. Biochemical Study of A Cancer Driver Fusion Protein, DnaJB1-PKA. FASEB J 2017; 31(1_supplement): 713-770..
[44]
McCarthy MM, Pick E, Kluger Y, et al. HSP90 as a marker of progression in melanoma. Ann Oncol 2008; 19(3): 590-4.
[http://dx.doi.org/10.1093/annonc/mdm545] [PMID: 18037622]
[45]
Radons J, Multhoff G. Immunostimulatory functions of membrane-bound and exported heat shock protein 70. Exerc Immunol Rev 2005; 11(1): 17-33.
[PMID: 16385841]
[46]
Shipp C, Weide B, Derhovanessian E, Pawelec G. Hsps are up-regulated in melanoma tissue and correlate with patient clinical parameters. Cell Stress Chaperones 2013; 18(2): 145-54.
[http://dx.doi.org/10.1007/s12192-012-0363-1] [PMID: 22872370]
[47]
Abubaker J, Tiss A, Abu-Farha M, et al. DNAJB3/HSP-40 cochaperone is downregulated in obese humans and is restored by physical exercise. PLoS One 2013; 8(7)e69217
[http://dx.doi.org/10.1371/journal.pone.0069217] [PMID: 23894433]
[48]
Vahid S, Thaper D, Gibson KF, Bishop JL, Zoubeidi A. Molecular chaperone Hsp27 regulates the Hippo tumor suppressor pathway in cancer. Sci Rep 2016; 6: 31842.
[http://dx.doi.org/10.1038/srep31842] [PMID: 27555231]
[49]
Chatterjee S, Burns TF. Targeting heat shock proteins in cancer: a promising therapeutic approach. Int J Mol Sci 2017; 18(9): 1978.
[http://dx.doi.org/10.3390/ijms18091978] [PMID: 28914774]
[50]
Choi S-K, Kam H, Kim K-Y, Park SI, Lee Y-S. Targeting Heat Shock Protein 27 in Cancer: A Druggable Target for Cancer Treatment? Cancers (Basel) 2019; 11(8): 1195.
[http://dx.doi.org/10.3390/cancers11081195] [PMID: 31426426]
[51]
Batulan Z, Pulakazhi Venu VK, Li Y, et al. Extracellular release and signaling by heat shock protein 27: role in modifying vascular inflammation. Front Immunol 2016; 7: 285.
[http://dx.doi.org/10.3389/fimmu.2016.00285] [PMID: 27507972]
[52]
Pockley AG, Henderson B. Extracellular cell stress (heat shock) proteins—immune responses and disease: an overview. Philosophical Transactions of the Royal Society B: Biological Sciences 2017; 373(1738): 20160522...
[53]
Zhu Z, Reiser G. The small heat shock proteins, especially HspB4 and HspB5 are promising protectants in neurodegenerative diseases. Neurochem Int 2018; 115: 69-79.
[http://dx.doi.org/10.1016/j.neuint.2018.02.006] [PMID: 29425965]
[54]
Li F, Xiao H, Hu Z, Zhou F, Yang B. Exploring the multifaceted roles of heat shock protein B8 (HSPB8) in diseases. Eur J Cell Biol 2018; 97(3): 216-29.
[http://dx.doi.org/10.1016/j.ejcb.2018.03.003] [PMID: 29555102]
[55]
Thuringer D, Jego G, Wettstein G, et al. Extracellular HSP27 mediates angiogenesis through Toll-like receptor 3. FASEB J 2013; 27(10): 4169-83.
[http://dx.doi.org/10.1096/fj.12-226977] [PMID: 23804239]
[56]
Glavan TM, Pavelic J. The exploitation of Toll-like receptor 3 signaling in cancer therapy. Curr Pharm Des 2014; 20(42): 6555-64.
[http://dx.doi.org/10.2174/1381612820666140826153347] [PMID: 25341932]
[57]
Wang X, Chen M, Zhou J, Zhang X. HSP27, 70 and 90, anti-apoptotic proteins, in clinical cancer therapy. (Review) Int J Oncol 2014; 45(1): 18-30.
[http://dx.doi.org/10.3892/ijo.2014.2399] [PMID: 24789222]
[58]
Acunzo J, Katsogiannou M, Rocchi P. Small heat shock proteins HSP27 (HspB1), αB-crystallin (HspB5) and HSP22 (HspB8) as regulators of cell death. Int J Biochem Cell Biol 2012; 44(10): 1622-31.
[http://dx.doi.org/10.1016/j.biocel.2012.04.002] [PMID: 22521623]
[59]
Havasi A, Li Z, Wang Z, et al. Hsp27 inhibits Bax activation and apoptosis via a phosphatidylinositol 3-kinase-dependent mechanism. J Biol Chem 2008; 283(18): 12305-13.
[http://dx.doi.org/10.1074/jbc.M801291200] [PMID: 18299320]
[60]
Aldrian S, Kindas-Mügge I, Trautinger F, et al. Overexpression of Hsp27 in a human melanoma cell line: regulation of E-cadherin, MUC18/MCAM, and plasminogen activator (PA) system. Cell Stress Chaperones 2003; 8(3): 249-57.
[http://dx.doi.org/10.1379/1466-1268(2003)008<0249:OOHIAH>2.0.CO;2] [PMID: 14984058]
[61]
Aldrian S, Trautinger F, Fröhlich I, Berger W, Micksche M, Kindas-Mügge I. Overexpression of Hsp27 affects the metastatic phenotype of human melanoma cells in vitro. Cell Stress Chaperones 2002; 7(2): 177-85.
[http://dx.doi.org/10.1379/1466-1268(2002)007<0177:OOHATM>2.0.CO;2] [PMID: 12380685]
[62]
Jin C, Cleveland JC, Ao L, et al. Human myocardium releases heat shock protein 27 (HSP27) after global ischemia: the proinflammatory effect of extracellular HSP27 through toll-like receptor (TLR)-2 and TLR4. Mol Med 2014; 20(1): 280-9.
[http://dx.doi.org/10.2119/molmed.2014.00058] [PMID: 24918749]
[63]
Wang B, Chen Z, Yu F, et al. Hsp90 regulates autophagy and plays a role in cancer therapy. Tumour Biol 2016; 37(1): 1-6.
[http://dx.doi.org/10.1007/s13277-015-4142-3] [PMID: 26432328]
[64]
Baumhof P. Google Patents 2015.
[65]
Amadori M. The Innate Immune Response to Noninfectious Stressors: Human and Animal Models. Academic Press 2016.
[66]
Tang AC, Rahavi SM, Fung S-Y, et al. Combination therapy with proteasome inhibitors and TLR agonists enhances tumour cell death and IL-1β production. Cell Death Dis 2018; 9(2): 162.
[http://dx.doi.org/10.1038/s41419-017-0194-1] [PMID: 29415982]
[67]
Saito K, Kukita K, Kutomi G, et al. Heat shock protein 90 associates with Toll-like receptors 7/9 and mediates self-nucleic acid recognition in SLE. Eur J Immunol 2015; 45(7): 2028-41.
[http://dx.doi.org/10.1002/eji.201445293] [PMID: 25871979]
[68]
Prodromou C. Mechanisms of Hsp90 regulation. Biochem J 2016; 473(16): 2439-52.
[http://dx.doi.org/10.1042/BCJ20160005] [PMID: 27515256]
[69]
Ito T, Suzuki T, Sakabe J-i, et al. Plasmacytoid dendritic cells as a possible key player to initiate alopecia areata in the C3H/HeJ mouse. Allergol Int 2019.
[PMID: 31431342]
[70]
Petes C, Odoardi N, Gee K. The toll for trafficking: toll-like receptor 7 delivery to the endosome. Front Immunol 2017; 8: 1075.
[http://dx.doi.org/10.3389/fimmu.2017.01075] [PMID: 28928743]
[71]
Tamura Y, Yoneda A, Takei N, et al. Chaperokine Activity of Heat Shock Proteins. Springer 2019; pp. 279-97.
[http://dx.doi.org/10.1007/978-3-030-02254-9_13]
[72]
Nativel B, Planesse C, Gasque P, et al. In Chaperokine Activity of Heat Shock Proteins. Springer 2019; pp. 57-80.
[http://dx.doi.org/10.1007/978-3-030-02254-9_3]
[73]
Cappello F. Chaperones. Springer 2018; pp. 293-305.
[74]
Şelli ME, Wick G, Wraith DC, Newby AC. Autoimmunity to HSP60 during diet induced obesity in mice. Int J Obes 2017; 41(2): 348-51.
[http://dx.doi.org/10.1038/ijo.2016.216] [PMID: 27899808]
[75]
Marino Gammazza A, Macaluso F, Di Felice V, Cappello F, Barone R. Hsp60 in skeletal muscle fiber biogenesis and homeostasis: From physical exercise to skeletal muscle pathology. Cells 2018; 7(12): 224.
[http://dx.doi.org/10.3390/cells7120224] [PMID: 30469470]
[76]
de Graaf R, Kloppenburg G, Kitslaar PJ, Bruggeman CA, Stassen F. Human heat shock protein 60 stimulates vascular smooth muscle cell proliferation through Toll-like receptors 2 and 4. Microbes Infect 2006; 8(7): 1859-65.
[http://dx.doi.org/10.1016/j.micinf.2006.02.024] [PMID: 16843693]

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy