Abstract
Metastasis, whether regional or distant, remains the main cause of morbidity and recurrence in oral cancer. The accumulating evidence suggests that inflammatory mediators are strong drivers for cancer progression and spread. However, the precise role of these inflammatory mediators in mediating specific metastatic stage is poorly understood due to lack of integration/validation of experimental research data and the clinical trials, i.e., the data produced from research is not translated to clinical therapeutic targets. This, in turn, results in the lack of developing reliable biomarker that can be used for accurate diagnosis/prognosis of the tumour spread. We have performed a systematic review to assess the role of inflammatory mediators as potential markers for diagnosis/prognosis of oral squamous cell carcinoma (OSCC) metastasis. We carried out a systematic search the PubMed, Web of Science, Embase and Scopus databases under the guidelines for Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Australian National Health and Medical Research Council (NHMRC). Articles were divided into two groups; experimental (in-vivo) and clinical studies. The REporting recommendations for tumour MARKer prognostic studies Scale (REMARK) was used to assess the quality of the studies for the clinical search while Animal research: Reporting In-vivo experiments (ARRIVE) guidelines were used to assess the quality of the animal studies. Sixteen articles in the clinical group and four articles in the experimental group were included in the final review. We identified nine inflammatory mediators; CXCR4, CXCL12 (SDF-1), CCR7, IL-6, IL-18, CCL20 (MIP-3), CXCL1 (GRO-1), CCL3, CXCR2. This panel of inflammatory mediators can provide a framework for hypothesis testing of the potential value of these mediators in metastatic prognosis. We recommend carrying a large cohort study with data pooling for adequate assessment and testing of the inflammatory panel of mediators.
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References
Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM (2010) Estimates of worldwide burden of cancer in 2008: Globocan 2008. Int J Cancer 127(12):2893–2917
Howlader N (2011) Seer cancer statistics review, 1975–2008. http://seer.cancer.gov/csr/1975_2008/
Yu X (2011) Epidemiology of cancer recurrence, second primary cancer, and comorbidity among cancer survivors health services for cancer survivors. Springer, New York, pp 277–297
Shah I, Sefvan O, Luqman U, Ibrahim W, Mehmood S, Alamgir W (2010) Clinical stage of oral cancer patients at the time of initial diagnosis. J Ayub Med Coll Abbottabad 22(3):61–63
Silverman S (2003) Oral cancer, vol 1. PMPH-USA, Raleigh
Warnakulasuriya S (2009) Global epidemiology of oral and oropharyngeal cancer. Oral Oncol 45(4–5):309–316
Amit M, Yen T, Liao C, Binenbaum Y, Chaturvedi P, Agarwal J, Kowalski L, Ebrahimi A, Clark J, Cernea C (2013) Clinical nodal stage is a significant predictor of outcome in patients with oral cavity squamous cell carcinoma and pathologically negative neck metastases: results of the international consortium for outcome research. Ann Surg Oncol 20(11):3575–3581
Massano J, Regateiro FS, Januário G, Ferreira A (2006) Oral squamous cell carcinoma: Review of prognostic and predictive factors. Oral Surg Oral Med Oral Pathol Oral Radiol Endodontol 102(1):67–76
Pulte D, Brenner H (2010) Changes in survival in head and neck cancers in the late 20th and early 21st century: a period analysis. Oncologist 15(9):994–1001
El-Naaj IA, Leiser Y, Shveis M, Sabo E, Peled M (2011) Incidence of oral cancer occult metastasis and survival of t1-t2n0 oral cancer patients. J Oral Maxillofac Surg 69(10):2674–2679
Furness S, Glenny AM, Worthington HV, Pavitt S, Oliver R, Clarkson JE, Macluskey M, Chan KK, Conway DI (2011) Interventions for the treatment of oral cavity and oropharyngeal cancer: chemotherapy. Cochrane Database Syst Rev 4:CD006386
Pignon J-P, Le Maitre A, Maillard E, Bourhis J (2009) Meta-analysis of chemotherapy in head and neck cancer (mach-nc): an update on 93 randomised trials and 17,346 patients. Radiother Oncol 92(1):4–14
Chiang AC, Massagué J (2008) Molecular basis of metastasis. N Engl J Med 359(26):2814–2823
Fidler IJ (2003) The pathogenesis of cancer metastasis: the seed and soil hypothesis revisited. Nat Rev Cancer 3(6):453–458
Brooks SA, Lomax-Browne HJ, Carter TM, Kinch CE, Hall DM (2010) Molecular interactions in cancer cell metastasis. Acta Histochem 112(1):3–25
Zavadil J, Haley J, Kalluri R, Muthuswamy SK, Thompson E (2008) Epithelial-mesenchymal transition. AACR, Philadelphia
Bergers G, Benjamin LE (2003) Tumorigenesis and the angiogenic switch. Nat Rev Cancer 3(6):401–410
Wyckoff JB, Jones JG, Condeelis JS, Segall JE (2000) A critical step in metastasis: In vivo analysis of intravasation at the primary tumor. Can Res 60(9):2504–2511
Nguyen DX, Bos PD, Massagué J (2009) Metastasis: From dissemination to organ-specific colonization. Nat Rev Cancer 9(4):274–284
Madsen CD, Sahai E (2010) Cancer dissemination—lessons from leukocytes. Dev Cell 19(1):13–26
Wu Y, Zhou BP (2009) Inflammation: a driving force speeds cancer metastasis. Cell Cycle 8(20):3267–3273
Desmoulière A (2008) Tumors: Wounds that do not heal. Similarities between tumor stroma generation and wound healing. In: Paper presented at the 2nd Scar meeting
Coussens LM, Werb Z (2002) Inflammation and cancer. Nature 420(6917):860–867
Perwez Hussain S, Harris CC (2007) Inflammation and cancer: an ancient link with novel potentials. Int J Cancer 121(11):2373–2380
Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144(5):646–674
McShane LM, Altman DG, Sauerbrei W, Taube SE, Gion M, Clark GM (2005) Reporting recommendations for tumor marker prognostic studies. J Clin Oncol 23(36):9067–9072
Kilkenny C, Browne W, Cuthill IC, Emerson M, Altman DG (2010) Animal research: reporting in vivo experiments: the arrive guidelines. Br J Pharmacol 160(7):1577–1579
Dupaul-Chicoine J, Saleh M (2013) Inflammatory mediators in tumorigenesis and metastasis. Experimental and clinical metastasis. Springer, New York, pp 101–127
Balkwill F (2004) Cancer and the chemokine network. Nat Rev Cancer 4(7):540–550
Ishikawa T, Nakashiro K, Hara S, Klosek SK, Li C, Shintani S, Hamakawa H (2006) Cxcr4 expression is associated with lymph-node metastasis of oral squamous cell carcinoma. Int J Oncol 28(1):61–66
Oliveira-Neto HH, Silva ET, Leles CR, Mendonça EF, Alencar RdC, Silva TA, Batista AC (2008) Involvement of cxcl12 and cxcr4 in lymph node metastases and development of oral squamous cell carcinomas. Tumor Biol 29(4):262–271
Uchida D, Begum N-M, Almofti A, Nakashiro K-i, Kawamata H, Tateishi Y, Hamakawa H, Yoshida H, Sato M (2003) Possible role of stromal-cell-derived factor-1/cxcr4 signaling on lymph node metastasis of oral squamous cell carcinoma. Exp Cell Res 290(2):289–302
Meng X, Wuyi L, Yuhong X, Xinming C (2010) Expression of cxcr4 in oral squamous cell carcinoma: correlations with clinicopathology and pivotal role of proliferation. J Oral Pathol Med 39(1):63–68
Albert S, Hourseau M, Halimi C, Serova M, Descatoire V, Barry B, Couvelard A, Riveiro ME, Tijeras-Raballand A, de Gramont A (2012) Prognostic value of the chemokine receptor cxcr4 and epithelial-to-mesenchymal transition in patients with squamous cell carcinoma of the mobile tongue. Oral Oncol 48(12):1263–1271
Lee J-I, Jin B-H, Kim M-A, Yoon H-J, Hong S-P, Hong S-D (2009) Prognostic significance of cxcr-4 expression in oral squamous cell carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol Endodontol 107(5):678–684
Uchida D, Onoue T, Tomizuka Y, Begum NM, Miwa Y, Yoshida H, Sato M (2007) Involvement of an autocrine stromal cell–derived factor-1/cxcr4 system on the distant metastasis of human oral squamous cell carcinoma. Mol Cancer Res 5(7):685–694
Uchida D, Begum NM, Tomizuka Y, Bando T, Almofti A, Yoshida H, Sato M (2004) Acquisition of lymph node, but not distant metastatic potentials, by the overexpression of cxcr4 in human oral squamous cell carcinoma. Lab Invest 84(12):1538–1546. https://doi.org/10.1038/labinvest.3700190
Förster R, Davalos-Misslitz AC, Rot A (2008) Ccr7 and its ligands: balancing immunity and tolerance. Nat Rev Immunol 8(5):362–371
Mburu YK, Wang J, Wood MA, Walker WH, Ferris RL (2006) Ccr7 mediates inflammation-associated tumor progression. Immunol Res 36(1–3):61–72
Xia X, Liu K, Zhang H, Shang Z (2015) Correlation between ccr7 expression and lymph node metastatic potential of human tongue carcinoma. Oral Dis 21(1):123–131
Shang ZJ, Liu K, Shao Z (2009) Expression of chemokine receptor ccr7 is associated with cervical lymph node metastasis of oral squamous cell carcinoma. Oral Oncol 45(6):480–485
Scheller J, Chalaris A, Schmidt-Arras D, Rose-John S (2011) The pro-and anti-inflammatory properties of the cytokine interleukin-6. Biochim Biophys Acta 1813(5):878–888
Schafer ZT, Brugge JS (2007) Il-6 involvement in epithelial cancers. J Clin Investig 117(12):3660–3663
Shinriki S, Jono H, Ueda M, Ota K, Ota T, Sueyoshi T, Oike Y, Ibusuki M, Hiraki A, Nakayama H (2011) Interleukin-6 signalling regulates vascular endothelial growth factor-c synthesis and lymphangiogenesis in human oral squamous cell carcinoma. J Pathol 225(1):142–150
Wang YF, Chang SY, Tai SK, Li WY, Wang LS (2002) Clinical significance of interleukin-6 and interleukin-6 receptor expressions in oral squamous cell carcinoma. Head Neck 24(9):850–858
Tsai HT, Hsin CH, Hsieh YH, Tang CH, Yang SF, Lin CW, Chen MK (2013) Impact of interleukin-18 polymorphisms − 607a/c and − 137 g/c on oral cancer occurrence and clinical progression. PLoS ONE 8(12):e83572. https://doi.org/10.1371/journal.pone.0083572
Shintani S, Ishikawa T, Nonaka T, Li C, Nakashiro K-i, Wong DT, Hamakawa H (2004) Growth-regulated oncogene-1 expression is associated with angiogenesis and lymph node metastasis in human oral cancer. Oncology 66(4):316–322
Ghadjar P, Rubie C, Aebersold DM, Keilholz U (2009) The chemokine ccl20 and its receptor ccr6 in human malignancy with focus on colorectal cancer. Int J Cancer 125(4):741–745
Wang B, Shi L, Sun X, Wang L, Wang X, Chen C (2016) Production of ccl 20 from lung cancer cells induces the cell migration and proliferation through pi 3k pathway. J Cell Mol Med 20(5):920–929
Chang K-P, Kao H-K, Yen T-C, Chang Y-L, Liang Y, Liu S-C, Lee L-Y, Chang Y-L, Kang C-J, Chen I-H (2011) Overexpression of macrophage inflammatory protein-3α in oral cavity squamous cell carcinoma is associated with nodal metastasis. Oral Oncol 47(2):108–113
Baba T, Mukaida N (2014) Role of macrophage inflammatory protein (mip)-1α/ccl3 in leukemogenesis. Mol Cell Oncol 1(1):e29899
De Oliveira-Neto HH, Watanabe S, Mendonça EF, Batista AC (2007) Dual role of ccl3/ccr1 in oral squamous cell carcinoma: implications in tumor metastasis and local host defense. Oncol Rep 18:1107–1113
Allen F, Rauhe P, Askew D, Tong AA, Nthale J, Eid S, Myers JT, Tong C, Huang AY (2017) Ccl3 enhances antitumor immune priming in the lymph node via ifnγ with dependency on natural killer cells. Front Immunol 8:1390
Ha H, Debnath B, Neamati N (2017) Role of the cxcl8-cxcr1/2 axis in cancer and inflammatory diseases. Theranostics 7(6):1543
Jaffer T, Ma D (2016) The emerging role of chemokine receptor cxcr2 in cancer progression. Transl Cancer Res 5(4):S616–S628
Steele CW, Karim SA, Leach JD, Bailey P, Upstill-Goddard R, Rishi L, Foth M, Bryson S, McDaid K, Wilson Z (2016) Cxcr2 inhibition profoundly suppresses metastases and augments immunotherapy in pancreatic ductal adenocarcinoma. Cancer Cell 29(6):832–845
Qian Y, Wang Y, Li DS, Zhu YX, Lu ZW, Ji QH, Yang G (2014) The chemokine receptor-cxcr2 plays a critical role in the invasion and metastases of oral squamous cell carcinoma in vitro and in vivo. J Oral Pathol Med 43(9):658–666
Shrihari T (2017) Dual role of inflammatory mediators in cancer. Ecancermedicalscience 11:721
Guan X (2015) Cancer metastases: challenges and opportunities. Acta Pharm Sin B 5(5):402–418
Roca H, McCauley LK (2015) Inflammation and skeletal metastasis. BoneKEy Rep 4:706
Liu K, Lu X, Zhu YS, Le N, Kim H, Poh CF (2018) Plasma-derived inflammatory proteins predict oral squamous cell carcinoma. Front Oncol 8:585. https://doi.org/10.3389/fonc.2018.00585
Goertzen C, Mahdi H, Laliberte C, Meirson T, Eymael D, Gil-Henn H, Magalhaes M (2018) Oral inflammation promotes oral squamous cell carcinoma invasion. Oncotarget 9(49):29047–29063. https://doi.org/10.18632/oncotarget.25540
Schaller TH, Batich KA, Suryadevara CM, Desai R, Sampson JH (2017) Chemokines as adjuvants for immunotherapy: implications for immune activation with ccl3. Expert Review Clin Immunol 13(11):1049–1060
Yan J, Wang Z-Y, Yang H-Z, Liu H-Z, Mi S, Lv X-X, Fu X-M, Yan H-M, Zhang X-W, Zhan Q-M (2011) Timing is critical for an effective anti-metastatic immunotherapy: the decisive role of ifnγ/stat1-mediated activation of autophagy. PLoS ONE 6(9):e24705
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Elhousiny, M., Miller, K., Ariyawadana, A. et al. Identification of inflammatory mediators associated with metastasis of oral squamous cell carcinoma in experimental and clinical studies: systematic review. Clin Exp Metastasis 36, 481–492 (2019). https://doi.org/10.1007/s10585-019-09994-x
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DOI: https://doi.org/10.1007/s10585-019-09994-x