Characterization of Wingless-Type signaling pathway proteins in odontogenic keratocyst and ameloblastoma
DOI:
https://doi.org/10.5935/2525-5711.20190021Keywords:
Odontogenic Cysts, odontogenic Tumors, Wnt signaling pathwayAbstract
Introduction: The Wnt signaling pathway is directly related to the development process of odontogenic keratocysts (OKC) and ameloblastomas (AM). However, the molecular mechanisms involved in the genesis and the activation process of the Wnt pathway of these tumors still need to be elucidated. Objective: To evaluate the immunohistoche- mical expression of Wingless-type (Wnt) proteins in OKC and AM. Materials and methods: Immunohistochemical staining was performed using antibodies against Wnt1, Wnt5a, SUFU and β-catenin proteins in cases of odontogenic keratocysts (n = 11) and ameloblastomas (n = 13). The analysis was performed by analysing staining intensity in both epithelial cells and fibroblasts. Results: Epithelial cells exhibited predominance of immunostaining in both lesions, with statistical association for SUFU markers in AM (p = 0.05) and β-catenin in OKC (p = 0.04). Wnt1 and Wnt5a had 100% immunostaining in epithelial cells and fibroblasts of AM and OKC, respectively. SUFU was significantly higher in OKC epithelial cells when compared to those in AM (p = 0.05). There was no statistical association in the immunosuppression of fibroblasts between AM and OKC, for all markers. Conclusion: The high intensity immunoexpression of Wnt1, β-catenin, SUFU and Wnt5a markers in OKC and AM epithelial cells suggests that Wnt signaling pathways, canonical and non-canonical, are activated and may contribute to the develop- ment, progression and aggressiveness of these lesions. On the other hand, it is suggested that the significant presence of SUFU in OKC epithelial cells confers a protective factor to this lesion, when compared to AM epithelial cells, indicating that the inactivation me- chanisms of the canonical pathway may be functioning. However, further investigations should be conducted to confirm such hypotheses.
References
Sharifi-Sistani N, Zartab H, Babakoohi S, Saghravanian N, Jamshidi S, Esmaili H et al. Immunohistochemical comparison of the expression of p53 and MDM2 proteins in ameloblastomas and keratocystic odontogenic tumors. J Craniofac Surg. 2011; 22:1652-6.
Bhagwat A, Barpande SR, Bhavthankar JD, Mandale MS, Humbe J, Singh PS. Odontogenic tumors: Review of 127 cases in Marathwada region of Maharashtra. J Oral Maxillofac Pathol. 2017; 21:457-8.
Kumamoto H, Ooya K. Immunohistochemical detection of beta-catenin and adenomatous polyposis coli in ameloblastomas. J Oral Pathol Med. 2005; 34:401-6.
Tanahashi J, Daa T, Yada N, Kashima K, Kondoh Y, Yokoyama S. Mutational analysis of Wnt signaling molecules in ameloblastoma with aberrant nuclear expression of β-catenin. J Oral Pathol Med. 2008; 37:565-70.
Chuah KS, Siar CH, Nakano K, Nagatsuke H, Khoo SP, NG KH et al. Wingless-type protein-1 (Wnt-1) expression in primary conventional and unicystic ameloblastomas and their recurrent tumors. J Hard Tissue Biol. 2009; 18:63-70.
Siar CH, Nagatsuka H, Han PP, Buery RR, Tsujigiwa H, Nakano K, et al. Differential expression of canonical and non-canonical Wnt ligands in ameloblastoma. J Oral Pathol Med. 2012; 41:332-9.
Arend RC, Londoño-Joshi AI, Straughn JM, Buchsbaum DJ. The Wnt/β-catenin pathway in ovarian cancer: a review. Gynecol Oncol. 2013; 131:772-9.
Grainger S, Willert K. Mechanisms of Wnt signaling and control. Wiley Interdiscip Rev Syst Biol Med. 2018; e1422. 9. Muzio L Lo, Muzio L Lo. A possible role for the Wnt-1 pathway in oral carcinogenesis. Oral Biol Med. 2001; 12:152-65.
Clevers H. Wnt/β-catenin signaling in development and disease. Cell. 2006; 127:469-80.
Kikuchi A, Yamamoto H, Kishida S. Multiplicity of the interactions of Wnt proteins and their receptors. Cell Signal. 2007; 19:659-71.
Wei Z, Zhong M, Guo Y, Wang Y, Ren M, Wang Z. Expression of β-catenin and AXIN2 in ameloblastomas. Wspolczesna Onkol. 2013; 17:250-6.
Obara N, Suzuki Y, Takeda M. Gene expression of β-catenin is up-regulated in inner dental epithelium and enamel knots during molar tooth morphogenesis in the mouse. Cell Tissue Res. 2006; 325:197-201.
Salahshor S, Naidoo R, Serra S, Shih W, Tsao MS, Chetty R et al. Frequent accumulation of nuclear E-cadherin and alterations in the Wnt signaling pathway in esophageal squamous cell carcinomas. Mod Pathol. 2008; 21:271-81.
Nelson WJ, Nusse R. Convergence of Wnt, β-catenin, and cadherin pathways. Science. 2004; 303:1483-7.
Krishnamurthy N, Kurzrock R. Targeting the Wnt/beta-catenin pathway in cancer: Update on effectors and inhibitors. Cancer Treat Rev. 2018; 62:50-60.
Meng X, Poon R, Zhang X, Cheah A, Ding Q, Hui CC et al. Suppressor of fused negatively regulates β-catenin signaling. J Biol Chem. 2001; 276:40113-9.
McDonald SL, Silver A. The opposing roles of Wnt-5a in cancer. Br J Cancer. 2009; 101:209-14.
Liu F, Millar SE. Wnt/β-catenin signaling in oral tissue development and disease. J Dent Res. 2010; 89:318-30.
Speight PM, Takata T. New tumour entities in the 4th edition of the World Health Organization Classification of Head and Neck tumours: odontogenic and maxillofacial bone tumours. Virchows Arch. 2017; 1-9.
Dultra FKAA, Barros AC, Schaer-Barbosa H, Figueiredo AL, Gurgel CAS, Ramos EAG, et al. Immunohistochemical assessment of CD1a-positive Langerhans cells and their relationship with E-cadherin in minor salivary gland tumors. J Oral Pathol Med. 2012; 41:47-53.
Hanahan D, Weinberg RA. Hallmarks of cancer: The next generation. Cell. 2011; 144:646-74.
Zustin J, Scheuer HA, Friedrich RE. Podoplanin expression in human tooth germ tissues and cystic odontogenic lesions: An immunohistochemical study. J Oral Pathol Med. 2010; 39:115-20.
Jiang C, Zhang Q, Shanti RM, Shi S, Chang TH, Carrasco L, et al. Mesenchymal stromal cell-derived interleukin-6 promotes epithelial – mesenchymal transition and acquisition of epithelial stem-like cell properties in ameloblastoma epithelial cells. Stem Cells. 2017; 35:2083-94.
Aurrekoetxea M, Irastorza I, García-Gallastegui P, Jiménez-Rojo L, Nakamura T, Yamada Y, et al. Wnt/β-catenin regulates the activity of epiprofin/Sp6, SHH, FGF, and BMP to coordinate the stages of odontogenesis. Front Cell Dev Biol. 2016; 4:1-14.
Syamala D, Suresh R, Janardhanan M, Savithri V, Anand PP, Jose A. Immunohistochemical evaluation of myofibroblasts in odontogenic cysts and tumors: a comparative study. J Oral Maxillofac Pathol. 2016; 20:208-13.
Nadalin MR, Fregnani ER, Silva-Sousa YTC, Da Cruz Perez DE. Presence of myofibroblasts and matrix metalloproteinase 2 in radicular cysts, dentigerous cysts, and keratocystic odontogenic tumors: a comparative immunohistochemical study. J Endod. 2012; 38:1363-7.
Gillies RJ, Gatenby RA. Adaptive landscapes and emergent phenotypes: Why do cancers have high glycolysis? J Bioenerg Biomembr. 2007; 39:251-7.
Bagul N. Dynamic role of myofibroblasts in oral lesions. World J Clin Oncol. 2015; 6:264.
Alves Pereira KM, Amaral BA, Santos BRM, Galvão HC, Freitas RA, Souza LB. Immunohistochemical expressionof E-cadherin and β-catenin in ameloblastomas and tooth germs. Oral Surgery, Oral Med Oral Pathol Oral Radiol Endodontology. 2010; 109:425-31.
Santos PPA, Nonaka CFW, Freitas RA, Pereira Pinto L, Souza LB. Immunohistochemical analysis of myofibroblasts, TGF-β1, and IFN-γ in epithelial odontogenic lesions. J Oral Pathol Med. 2017; 46:365-70.
Hakim SG, Kosmehl H, Sieg P, Trenkle T, Jacobsen HC, Benedek GA, et al. Altered expression of cell-cell adhesion molecules β-catenin/E-cadherin and related Wnt-signaling pathway in sporadic and syndromal keratocystic odontogenic tumors. Clin Oral Investig. 2011; 15:321-8.
Dutra SN, Pires FR, Armada L, Azevedo RS. Immunoexpression of Wnt/β-catenin signaling pathway proteins in ameloblastoma and calcifying cystic odontogenic tumor. J Clin Exp Dent. 2017; 9:e136-e140.
Wang GN, Zhong M, Chen YV, Ji J, Gao XQ, Wang TF. Expression of wnt1 in ameloblastoma and its significance. Oncol Lett. 2018; 16:1507-12.
Pukrop T, Binder C. The complex pathways of Wnt 5a in cancer progression. J Mol Med. 2008; 86:259-66.
Shimada Y, Katsube K ichi, Kabasawa Y, Morita K ichi, Omura K, Yamaguchi A, et al. Integrated Genotypic Analysis of Hedgehog-Related Genes Identifies Subgroups of Keratocystic Odontogenic Tumor with Distinct Clinicopathological Features. PLoS One. 2013; 8. doi:10.1371/journal.pone.0070995.
Guimarães DM, Antunes DM, Saturno JL, Massuda F, Paiva KBS, Nunes FD. Immunohistochemical expression of WNT5A and MMPs in odontogenic epithelial tumors and cysts. Acta Histochem. 2015; 117:667-74.
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Copyright (c) 1969 Gardênia de Matos Paraguassú, Viviane Palmeira da Silva, Clarissa Araújo Gurgel, Jean Nunes dos Santos, Maria Cristina Teixeira Cangussu, Ludmila de Faro Valverde, Luciana Maria Pedreira Ramalho
This work is licensed under a Creative Commons Attribution 4.0 International License.
