Role of Toll-like Receptor 4 on the Immune Escape of Human Oral Squamous Cell Carcinoma and Resistance of Cisplatin-induced Apoptosis

Overview

Journal Mol Cancer

Publisher Biomed Central

Specialties Molecular Biology
Oncology

Date 2012 May 16

PMID 22583829

Citations 39

Authors

Zujun Sun

Qingqiong Luo

Dongxia Ye

Wantao Chen

Fuxiang Chen

Affiliations

Soon will be listed here.

Abstract

Background: Toll-like receptor 4 (TLR4) is expressed on immune cells as a sensor that recognizes lipopolysaccharide (LPS), a microbial conserved component. It has recently been determined that the expression of TLR4 is also found in various types of tumor cells. Cisplatin is a widely used chemotherapeutic agent for oral squamous cell carcinoma (OSCC) treatment. However, the mechanisms responsible for cisplatin resistance are not well understood.

Results: The present study was designed to elucidate the role of TLR4 expression in human OSCC regarding immune escape and apoptotic resistance to cisplatin. TLR4 and the myeloid differentiation primary response gene 88 (MyD88) were highly expressed in OSCC cell lines. Upon LPS stimulation both NF-κB and p38 MAPK pathways were activated in OSCC cell lines, followed by the production of large quantities of IL-6, IL-8 and VEGF compared with human immortalized oral epithelia cells (HIOECs). OSCC cell lines were found to be resistant to cisplatin-mediated apoptosis after pretreatment with LPS.

Conclusions: Our results suggested that TLR4 was functionally expressed in human OSCC cells and development of resistance to cisplatin in human OSCC might occur through the mechanism involving TLR4 and its signaling pathway. Suppression of TLR4 and its signaling pathway might thus elevate sensitivity to cisplatin and potentially help improve the prognosis of patients with OSCC.

Citing Articles

Toll-like Receptors: Key Players in Squamous Cell Carcinoma Progression.

Smok-Kalwat J, Mertowska P, Mertowski S, Gozdz S, Grywalska E J Clin Med. 2024; 13(15).

PMID: 39124797 PMC: 11313009. DOI: 10.3390/jcm13154531.

Effects of Angiogenic Factors on the Epithelial-to-Mesenchymal Transition and Their Impact on the Onset and Progression of Oral Squamous Cell Carcinoma: An Overview.

Pomella S, Melaiu O, Dri M, Martelli M, Gargari M, Barillari G Cells. 2024; 13(15.

PMID: 39120324 PMC: 11311310. DOI: 10.3390/cells13151294.

Analysis of Selected Toll-like Receptors in the Pathogenesis and Advancement of Non-Small-Cell Lung Cancer.

Smok-Kalwat J, Mertowska P, Mertowski S, Gozdz S, Korona-Glowniak I, Kwasniewski W J Clin Med. 2024; 13(10).

PMID: 38792335 PMC: 11122486. DOI: 10.3390/jcm13102793.

Genetic Association of Toll-Like Receptor 4 (TLR4) Gene Polymorphism (rs4986790) With Oral Squamous Cell Carcinoma (OSCC): A Pilot Case-Control Study.

Gautam B, Pandi A, Smiline Girija A, Arumugam P, Priyadharsini V Cureus. 2024; 16(3):e56021.

PMID: 38606218 PMC: 11007480. DOI: 10.7759/cureus.56021.

Expression of Toll-like receptors in oral squamous cell carcinoma.

Rusanen P, Marttila E, Amatya S, Hagstrom J, Uittamo J, Reunanen J PLoS One. 2024; 19(4):e0300437.

PMID: 38593176 PMC: 11003673. DOI: 10.1371/journal.pone.0300437.

References

Harmey J, Bucana C, Lu W, Byrne A, McDonnell S, Lynch C . Lipopolysaccharide-induced metastatic growth is associated with increased angiogenesis, vascular permeability and tumor cell invasion. Int J Cancer. 2002; 101(5):415-22. DOI: 10.1002/ijc.10632. View

Macagno A, Molteni M, Rinaldi A, Bertoni F, Lanzavecchia A, Rossetti C . A cyanobacterial LPS antagonist prevents endotoxin shock and blocks sustained TLR4 stimulation required for cytokine expression. J Exp Med. 2006; 203(6):1481-92. PMC: 2118317. DOI: 10.1084/jem.20060136. View

Takeda K, Kaisho T, Akira S . Toll-like receptors. Annu Rev Immunol. 2003; 21:335-76. DOI: 10.1146/annurev.immunol.21.120601.141126. View

Vaquero J, Campbell J, Haque J, McMahan R, Riehle K, Bauer R . Toll-like receptor 4 and myeloid differentiation factor 88 provide mechanistic insights into the cause and effects of interleukin-6 activation in mouse liver regeneration. Hepatology. 2011; 54(2):597-608. PMC: 4247827. DOI: 10.1002/hep.24420. View

Duan Z, Feller A, Toh H, Makastorsis T, Seiden M . TRAG-3, a novel gene, isolated from a taxol-resistant ovarian carcinoma cell line. Gene. 1999; 229(1-2):75-81. DOI: 10.1016/s0378-1119(99)00042-6. View

Clinchy B, Fransson A, Druvefors B, Hellsten A, Hakansson A, Gustafsson B . Preoperative interleukin-6 production by mononuclear blood cells predicts survival after radical surgery for colorectal carcinoma. Cancer. 2007; 109(9):1742-9. DOI: 10.1002/cncr.22623. View

Zhong L, Pan H, Zhou X, Ye D, Zhang L, Yang X . Characteristics of a cancerous cell line, HIOEC-B(a)P-96, induced by benzo(a)pyrene from human immortalized oral epithelial cell line. Arch Oral Biol. 2008; 53(5):443-52. DOI: 10.1016/j.archoralbio.2007.12.002. View

McClure N, Healy D, Rogers P, Sullivan J, Beaton L, Haning Jr R . Vascular endothelial growth factor as capillary permeability agent in ovarian hyperstimulation syndrome. Lancet. 1994; 344(8917):235-6. DOI: 10.1016/s0140-6736(94)93001-5. View

Chen R, Alvero A, Silasi D, Mor G . Inflammation, cancer and chemoresistance: taking advantage of the toll-like receptor signaling pathway. Am J Reprod Immunol. 2007; 57(2):93-107. DOI: 10.1111/j.1600-0897.2006.00441.x. View

10.

Gabrilovich D, Ishida T, Oyama T, Ran S, Kravtsov V, Nadaf S . Vascular endothelial growth factor inhibits the development of dendritic cells and dramatically affects the differentiation of multiple hematopoietic lineages in vivo. Blood. 1998; 92(11):4150-66. View

11.

Penson R, Kronish K, Duan Z, Feller A, Stark P, Cook S . Cytokines IL-1beta, IL-2, IL-6, IL-8, MCP-1, GM-CSF and TNFalpha in patients with epithelial ovarian cancer and their relationship to treatment with paclitaxel. Int J Gynecol Cancer. 2001; 10(1):33-41. DOI: 10.1046/j.1525-1438.2000.00003.x. View

12.

Szajnik M, Szczepanski M, Czystowska M, Elishaev E, Mandapathil M, Nowak-Markwitz E . TLR4 signaling induced by lipopolysaccharide or paclitaxel regulates tumor survival and chemoresistance in ovarian cancer. Oncogene. 2009; 28(49):4353-63. PMC: 2794996. DOI: 10.1038/onc.2009.289. View

13.

Kawai T, Akira S . Signaling to NF-kappaB by Toll-like receptors. Trends Mol Med. 2007; 13(11):460-9. DOI: 10.1016/j.molmed.2007.09.002. View

14.

Szczepanski M, Czystowska M, Szajnik M, Harasymczuk M, Boyiadzis M, Kruk-Zagajewska A . Triggering of Toll-like receptor 4 expressed on human head and neck squamous cell carcinoma promotes tumor development and protects the tumor from immune attack. Cancer Res. 2009; 69(7):3105-13. PMC: 3708458. DOI: 10.1158/0008-5472.CAN-08-3838. View

15.

Hsu R, Chan C, Spicer J, Rousseau M, Giannias B, Rousseau S . LPS-induced TLR4 signaling in human colorectal cancer cells increases beta1 integrin-mediated cell adhesion and liver metastasis. Cancer Res. 2011; 71(5):1989-98. DOI: 10.1158/0008-5472.CAN-10-2833. View

16.

Huang B, Zhao J, Li H, He K, Chen Y, Chen S . Toll-like receptors on tumor cells facilitate evasion of immune surveillance. Cancer Res. 2005; 65(12):5009-14. DOI: 10.1158/0008-5472.CAN-05-0784. View

17.

Kojima M, Morisaki T, Izuhara K, Uchiyama A, Matsunari Y, Katano M . Lipopolysaccharide increases cyclo-oxygenase-2 expression in a colon carcinoma cell line through nuclear factor-kappa B activation. Oncogene. 2000; 19(9):1225-31. DOI: 10.1038/sj.onc.1203427. View

18.

Hefler L, Grimm C, Ackermann S, Malur S, Radjabi-Rahat A, Leodolter S . An interleukin-6 gene promoter polymorphism influences the biological phenotype of ovarian cancer. Cancer Res. 2003; 63(12):3066-8. View

19.

Lokshin A, Winans M, Landsittel D, Marrangoni A, Velikokhatnaya L, Modugno F . Circulating IL-8 and anti-IL-8 autoantibody in patients with ovarian cancer. Gynecol Oncol. 2006; 102(2):244-51. DOI: 10.1016/j.ygyno.2005.12.011. View

20.

Akira S, Uematsu S, Takeuchi O . Pathogen recognition and innate immunity. Cell. 2006; 124(4):783-801. DOI: 10.1016/j.cell.2006.02.015. View