Citation Information :
Yadahalli R, Sarode GS, Patil S. Significance of CC Group of Chemokines in Oral Squamous Cell Carcinoma and Oral Potential Malignant Disorders: A Review. World J Dent 2021; 12 (2):160-165.
Aim and objective: The underlying association of the CC group of cytokines and its systemic role in fibrosis.
Background: Chemokines the secretory proteins are produced by leukocytes and other tissue cells integrally or after induction, function regionally in a paracrine or autocrine manner.
Review results: Functionally chemokines are split into constitutive (homeostatic, housekeeping, or lymphoid) and inducible (inflammatory) ones presented by cells, based on the conditions of their production or can be both. Chemotactic proteins have a vital role in host defense activities by developing and maintaining innate and acquired immunity. Importantly, chemokines also participate in wound healing, angiogenesis/angiostasis, lymphocyte polarization, apoptosis, fibrosis, and the development and metastasis of tumors.
Conclusion: It reviews the CC chemokine in health and physiology then the role of it in inflammation, immune diseases, oral potentially malignant disorders (OPMDs), and development and metastasis of the tumor.
Clinical significance: The diseases where inflammation and fibrosis play an important role continue to grow and therefore the need for safe and effective anti-fibrotic therapies is great and is also likely to increase.
Baggiolini M. Chemokines in pathology and medicine. J Intern Med 2001;250(2):91–104. DOI: 10.1046/j.1365-2796.2001.00867.x.
Bachelerie F, Ben-Baruch A, Burkhardt AM, et al. International Union of Basic and Clinical Pharmacology. Update on the extended family of chemokine receptors and introducing a new nomenclature for atypical chemokine receptors. Pharmacol Rev 2014;66(1):1–79. DOI: 10.1124/pr.113.007724.
Raman D, Sobolik-Delmaire T, Richmond A. Chemokines in health and disease. Exp Cell Res 2011;317(5):575–589. DOI: 10.1016/j.yexcr.2011.01.005.
Sarode G, Sarode S, Deshmukh R, et al. Myofibroblasts could be recruited in a chemokine (C-C motif) ligand 2-dependent manner in pathogenesis of oral submucous fibrosis. J Oral Path and Med 2017;46(6):443–447.
Murakami T, Cardones AR, Hwang ST. Chemokine receptors and melanoma metastasis. J Dermatol Sci 2004;36(2):71–78. DOI: 10.1016/j.jdermsci.2004.03.002.
Roy I, Evans DB, Dwinell MB. Chemokines and chemokine receptors: update on utility and challenges for the clinician. Surgery 2014;155(6):961–973. DOI: 10.1016/j.surg.2014.02.006.
Hannan NJ, Jones RL, White CA, et al. The chemokines, CX3CL1, CCL14, and CCL4, promote human trophoblast migration at the feto-maternal interface. Biol Reprod 2006;74(5):896–904. DOI: 10.1095/biolreprod.105.045518.
Hess AP, Hamilton AE, Talbi S, et al. Decidual stromal cell response to paracrine signals from the trophoblast: amplification of immune and angiogenic modulators. Biol Reprod 2007;76(1):102–117. DOI: 10.1095/biolreprod.106.054791.
Esche C, Stellato C, Beck LA. Chemokines: key players in innate and adaptive immunity. J Invest Dermatol 2005;125(4):615–628. DOI: 10.1111/j.0022-202X.2005.23841.x.
Cyster JG. Chemokines and cell migration in secondary lymphoid organs. Science 1999;286(5447):2098–2102. DOI: 10.1126/science.286.5447.2098.
Ogawa N, Ping L, Zhenjun L, et al. Involvement of the interferon-gamma-induced T cell-attracting chemokines, interferon-gamma-inducible 10-kd protein (CXCL10) and monokine induced by interferon-gamma (CXCL9), in the salivary gland lesions of patients with Sjögren's syndrome. Arthritis Rheum 2002;46(10):2730–2741. DOI: 10.1002/art.10577.
Vecchi A, Massimiliano L, Ramponi S, et al. Differential responsiveness to constitutive vs. inducible chemokines of immature and mature mouse dendritic cells. J Leukoc Biol 1999;66(3):489–494. DOI: 10.1002/jlb.66.3.489.
Inokuma D, Abe R, Fujita Y, et al. CTACK/CCL27 accelerates skin regeneration via accumulation of bone marrow derived keratinocytes. Stem Cells 2006;24:2810–2816.
Keeley EC, Mehrad B, Strieter RM. Chemokines as mediators of neovascularization. Arterioscler Thromb Vasc Biol 2008;28(11):1928–1936. DOI: 10.1161/ATVBAHA.108.162925.
Strasly M, Doronzo G, Capello P, et al. CCL16 activates an angiogenic program in vascular endothelial cells. Blood 2004;103(1):40–49. DOI: 10.1182/blood-2003-05-1387.
Kawashima D, Oshitani N, Jinno Y, et al. Augmented expression of secondary lymphoid tissue chemokine and EBI1 ligand chemokine in Crohn's disease. J Clin Pathol 2005;58(10):1057–1063. DOI: 10.1136/jcp.2004.024828.
Ogawa H, Iimura M, Eckmann L, et al. Regulated production of the chemokine CCL28 in human colon epithelium. Am J Physiol 2004;287(5):1062–1069. DOI: 10.1152/ajpgi.00162.2004.
Mabuchi T, Singh TP, Takekoshi T, et al. CCR6 is required for epidermal trafficking of gammadelta-T cells in an IL-23-induced model of psoriasi-form dermatitis. J Invest Dermatol 2013;133(1):164–171. DOI: 10.1038/jid.2012.260.
Rottman JB, Smith TL, Ganley KG, et al. Potential role of the chemokine receptors CXCR3, CCR4, and the integrin alphaEbeta7 in the pathogenesis of psoriasis vulgaris. Lab Invest 2001;81(3):335–347. DOI: 10.1038/labinvest.3780242.
Homey B, Dieu-Nosjean MC, Wiesenborn A, et al. Up-regulation of macrophage inflammatory protein-3α/CCL20 and CC chemokine receptor 6 in psoriasis. J Immunol 2000;164(12):6621–6632. DOI: 10.4049/jimmunol.164.12.6621.
Mahad DJ, Trebst C, Kivisäkk P, et al. Expression of chemokine receptors CCR1 and CCR5 reflects differential activation of mononuclear phagocytes in pattern II and pattern III multiple sclerosis lesions. J Neuropathol Exp Neurol 2004;63(3):262–273. DOI: 10.1093/jnen/63.3.262.
Cardona S, Garcia J, Cardona A. The fine balance of chemokines during disease: trafficking, inflammation, and homeostasis. Methods Mol Biol 2013;1013:1–16.
Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin 2011;61(2):69–90. DOI: 10.3322/caac.20107.
Qin S, Rottman JB, Myers P, et al. The chemokine receptors CXCR3 and CCR5 mark subsets of T cells associated with certain inflammatory reactions. J Clin Invest 1998;101(4):746–754. DOI: 10.1172/JCI1422.
Loetscher P, Uguccioni M, Bordoli L, et al. CCR5 is characteristic of Th1 lymphocytes. Nature 1998;391(6665):344–345. DOI: 10.1038/34814.
Little MC, Griffiths CE, Watson RE, et al. Oral mucosal keratinocytes express RANTES and ICAM-1, but not interleukin-8, in oral lichen planus and oral lichenoid reactions induced by amalgam fillings. Clin Exp Dermatol 2003;28(1):64–69. DOI: 10.1046/j.1365-2230.2003.01158.x.
Zhao ZZ, Sugerman PB, Walsh LJ, et al. Expression of RANTES and CCR1 in oral lichen planus and association with mast cell migration. J Oral Pathol Med 2002;31(3):158–162. DOI: 10.1034/j.1600-0714.2002.310306.x.
Ichimura M, Hiratsuka K, Ogura N, et al. Expression profile of chemokines and chemokine receptors in epithelial cell layers of oral lichen planus. J Oral Pathol Med 2006;35(3):167–174. DOI: 10.1111/j.1600-0714.2006.00402.x.
Shan J, Shan Li, Wang C, et al. Expression and biological functions of the CCL 5‐CCR 5 axis in oral lichen planus. Exp Dermat 2019;28(7):816–821. DOI: 10.1111/exd.13946.
Shan J, Shen C, Fang J, et al. Potential roles of the CCL 17-CCR 4 axis in immuno-pathogenesis of oral lichen planus. J Oral Pathol Med 2019;00:1–7.
Sandhu SK, Papadopoulos K, Fong PC, et al. A first-in-human, first-in-class, phase I study of carlumab (CNTO 888), a human monoclonal antibody against CC-chemokine ligand 2 in patients with solid tumors. Canc Chemother Pharmaco 2013;71(4):1041–1050. DOI: 10.1007/s00280-013-2099-8.
Pienta KJ, Machiels JP, Schrijvers D, et al. Phase 2 study of carlumab (CNTO 888), a human monoclonal antibody against CC-chemokine ligand 2 (CCL2), in metastatic castration-resistant prostate cancer. Invest New Drugs 2013;31(3):760–768. DOI: 10.1007/s10637-012-9869-8.
Ferreira FO, Ribeiro FLL, Batista AC, et al. Association of CCL2 with lymph node metastasis and macrophage infiltration in oral cavity and lip squamous cell carcinoma. Tumour Biol 2008;29(2):114–121. DOI: 10.1159/000137669.
Li X, Xu Q, Wu Y, et al. A CCL2/ROS autoregulation loop is critical for cancer-associated fibroblasts-enhanced tumor growth of oral squamous cell carcinoma. Carcinogenesis 2014;35(6):1362–1370. DOI: 10.1093/carcin/bgu046.
Bektas-Kayhan K, Unur M, Boy-Metin Z, et al. MCP-1 and CCR2 gene variants in oral squamous cell carcinoma. Oral Dis 2012;18(1):55–59. DOI: 10.1111/j.1601-0825.2011.01843.x.
Silva TA, Unur M, Boy-Metin Z, et al. Dual role of CCL3/CCR1 in oral squamous cell carcinoma: implications in tumor metastasis and local host defense. Oncol Rep 2007;18:1107–1113.
Chuang JY, Yang WH, Chen HT, et al. CCL5/CCR5 axis promotes the motility of human oral cancer cells. J Cell Physiol 2009;220(2):418–426. DOI: 10.1002/jcp.21783.
Tanyel CR, Cincin ZB, Gokcen-Rohlig B, et al. Effects of genetic variants of CCR5 chemokine receptors on oral squamous cell carcinoma. Genet Mol Res 2013;12(4):5714–5720. DOI: 10.4238/2013.November.18.20.
Weng CJ, Chien MH, Lin CW, et al. Effect of CC chemokine ligand 5 and CC chemokine receptor 5 genes polymorphisms on the risk and clinicopathological development of oral cancer. Oral Oncol 2010;46(10):767–772. DOI: 10.1016/j.oraloncology.2010.07.011.
Chakraborty K, Bose A, Goswami KK, et al. Dysregulated CC receptor/ligand in monocytes/macrophages from tongue squamous cell carcinoma patients is partially rectified by interferon α-2b. Hum Immunol 2012;73(1):38–47. DOI: 10.1016/j.humimm.2011.10.015.
Jung DW, Che ZM, Kim J, et al. Tumor-stromal crosstalk in invasion of oral squamous cell carcinoma: a pivotal role of CCL7. Int J Cancer 2010;127:332–344.
Shang ZJ, Liu K, Shao Z. Expression of chemokine receptor CCR7 is associated with cervical lymph node metastasis of oral squamous cell carcinoma. Oral Oncol 2009;45(6):480–485. DOI: 10.1016/j.oraloncology.2008.06.005.
Tsuzuki H, Takahashi N, Kojima A, et al. Oral and oropharyngeal squamous cell carcinomas expressing CCR7 have poor prognoses. Auris Nasus Larynx 2006;33(1):37–42. DOI: 10.1016/j.anl.2005.07.019.
Irino T, Takeuchi H, Matsuda S, et al. CC Chemokine receptor CCR7: a key molecule for lymph node metastasis in esophageal squamous cell carcinoma. BMC Canc 2014;14(1):291. DOI: 10.1186/1471-2407-14-291.
Li P, Zhao ZJ, Liu FY, et al. The chemokine receptor 7 regulates cell adhesion and migration via beta1 integrin in metastatic squamous cell carcinoma of the head and neck. Oncol Rep 2010;24:989–995.
Zhao ZJ, Liu FY, Li P, et al. CCL19-induced chemokine receptor 7 activates the phosphoinositide-3 kinase-mediated invasive pathway through Cdc42 in metastatic squamous cell carcinoma of the head and neck. Oncol Rep 2011;25:729–737.
Guo N, Liu F, Yang L, et al. Chemokine receptor 7 enhances cell chemotaxis and migration of metastatic squamous cell carcinoma of head and neck through activation of matrix metalloproteinase-9. Oncol Rep 2014;32(2):794–800. DOI: 10.3892/or.2014.3242.
Liu FY, Safdar J, Li ZN, et al. CCR7 regulates cell migration and invasion through MAPKs in metastatic squamous cell carcinoma of head and neck. Int J Onco 2014;45(6):2502–2510. DOI: 10.3892/ijo.2014.2674.
Jiang C, Yang D, Wang J. Correlations of abnormally upregulated CC chemokine ligand 18 (CCL18) with clinical stage and cervical lymph node metastasis status in serum and tumor tissue of patients with oral squamous cell carcinoma. Int J Clin Exp Pathol 2016;9(6):6317–6325.
Abiko Y, Nishimura M, Kusano K, et al. Expression of MIP-3alpha/CCL20, a macrophage inflammatory protein in oral squamous cell carcinoma. Arch Oral Biol 2003;48(2):171–175. DOI: 10.1016/S0003-9969(02)00167-X.
Chang KP, Kao HK, Yen TC, et al. Overexpression of macrophage inflammatory protein-3a in oral cavity squamous cell carcinoma s associated with nodal metastasis. Oral Oncol 2011;47(2):108–113. DOI: 10.1016/j.oraloncology.2010.11.012.
Wang H, Liang X, Li M, et al. Chemokine (CC motif) ligand 18 upregulates Slug expression to promote stem-cell like features by activating the mammalian target of rapamycin pathway in oral squamous cell carcinoma. Cancer Sci 2017;108(8):1584–1593. DOI: 10.1111/cas.13289.
Lien MY, Tsai HC, Chang AC, et al. Chemokine CCL4 induces vascular endothelial growth factor C expression and lymphangiogenesis by mir-195-3p in oral squamous cell carcinoma. Front Immunol 2018;9:412. DOI: 10.3389/fimmu.2018.00412.
Mao L, Zhuang R, Qin L, et al. CCL18 overexpression predicts a worse prognosis in oral squamous cell carcinoma (OSCC). Neoplasma 2020;67(3):700–706. DOI: 10.4149/neo_2020_190821N802.
Jiang X, Huang Z, Sun X, et al. CCL18-NIR1 promotes oral cancer cell growth and metastasis by activating the JAK2/STAT3 signaling pathway. BMC Cancer 2020;20(1):632. DOI: 10.1186/s12885-020-07073-z.