nach oben

Erschienen in:

01.12.2024 | Research

CLIC4 Function in the Epithelial-Mesenchymal Transition of Epithelial Odontogenic Lesions

verfasst von: Mariana Carvalho Xerez, Caio César da Silva Barros, Maurília Raquel de Souto Medeiros, Rodrigo Porpino Mafra, Hévio Freitas de Lucena, Éricka Janine Dantas da Silveira, Antonio de Lisboa Lopes Costa

Erschienen in: Head and Neck Pathology | Ausgabe 1/2024

Einloggen, um Zugang zu erhalten

Abstract

Background

Odontogenic lesions constitute a heterogeneous group of lesions. CLIC4 protein regulates different cellular processes, including epithelial-mesenchymal transition and fibroblast-myofibroblast transdifferentiation. This study analyzed CLIC4, E-cadherin, Vimentin, and α-SMA immunoexpression in epithelial odontogenic lesions that exhibit different biological behavior.

Methods

It analyzed the immunoexpression of CLIC4, E-cadherin, and Vimentin in the epithelial cells, as well as CLIC4 and α-SMA in the mesenchymal cells, of ameloblastoma (AM) (n = 16), odontogenic keratocyst (OKC) (n = 20), and adenomatoid odontogenic tumor (AOT) (n = 8). Immunoexpressions were categorized as score 0 (0% positive cells), 1 (< 25%), 2 (≥ 25% - < 50%), 3 (≥ 50% - < 75%), or 4 (≥ 75%).

Results

Cytoplasmic CLIC4 immunoexpression was higher in AM and AOT (p < 0.001) epithelial cells. Nuclear-cytoplasmic CLIC4 was higher in OKC’s epithelial lining (p < 0.001). Membrane (p = 0.012) and membrane-cytoplasmic (p < 0.001) E-cadherin immunoexpression were higher in OKC, while cytoplasmic E-cadherin expression was higher in AM and AOT (p < 0.001). Vimentin immunoexpression was higher in AM and AOT (p < 0.001). Stromal CLIC4 was higher in AM and OKC (p = 0.008). Similarly, α-SMA immunoexpression was higher in AM and OKC (p = 0.037). Correlations in these proteins’ immunoexpression were observed in AM and OKC (p < 0.05).

Conclusions

CLIC4 seems to regulate the epithelial-mesenchymal transition, modifying E-cadherin and Vimentin expression. In mesenchymal cells, CLIC4 may play a role in fibroblast-myofibroblast transdifferentiation. CLIC4 may be associated with epithelial odontogenic lesions with aggressive biological behavior.

Nur mit Berechtigung zugänglich

Vered M, Wright JM (2022) Update from the 5th Edition of the World Health Organization Classification of Head and Neck tumors: odontogenic and maxillofacial bone tumours. Head Neck Pathol 16:63–75. https://doi.org/10.1007/s12105-021-01404-7CrossRefPubMedPubMedCentral

Santos PPDA, Nonaka CFW, Freitas RDA, Pereira Pinto L, Souza LBD (2017) Immunohistochemical analysis of myofibroblasts, TGF -β1, and IFN ‐γ in epithelial odontogenic lesions. J Oral Pathol Med 46:365–370. https://doi.org/10.1111/jop.12494CrossRefPubMed

Mello FW, Melo G, Kammer PV, Speight PM, Rivero ERC (2019) Prevalence of odontogenic cysts and tumors associated with impacted third molars: a systematic review and meta-analysis. J Craniomaxillofac Surg 47:996–1002. https://doi.org/10.1016/j.jcms.2019.03.026CrossRefPubMed

Shukla A, Yuspa SH (2010) CLIC4 and Schnurri2: a dynamic duo in TGFβ signaling with broader implications in cellular homeostasis and disease. Nucleus 1:1441–1449. https://doi.org/10.4161/nucl.1.2.10920CrossRef

Yao Q, Qu X, Yang Q, Wei M, Kong B (2009) CLIC4 mediates TGF-beta1-induced fibroblast-to-myofibroblast transdifferentiation in ovarian cancer. Oncol Rep 22:541–548. https://doi.org/10.3892/or_00000469CrossRefPubMed

Suh KS, Malik M, Shukla A et al (2012) CLIC4 is a tumor suppressor for cutaneous squamous cell cancer. Carcinogenesis 2012;33:986–995. https://doi.org/10.1093/carcin/bgs115

Shukla A, Edwards R, Yang Y et al (2014) CLIC4 regulates TGF-β-dependent myofibroblast differentiation to produce a cancer stroma. Oncogene 33:842–850. https://doi.org/10.1038/onc.2013.18CrossRefPubMed

Gonzalez DM, Medici D (2014) Signaling mechanisms of the epithelial-mesenchymal transition. Sci Signal 7:re8. https://doi.org/10.1126/scisignal.2005189CrossRefPubMedPubMedCentral

Yoshida T, Ozawa Y, Kimura T et al (2014) Eribulin mesilate suppresses experimental metastasis of breast cancer cells by reversing phenotype from epithelial-mesenchymal transition (EMT) to mesenchymal-epithelial transition (MET) states. Br J Cancer 110:1497–1505. https://doi.org/10.1038/bjc.2014.80CrossRefPubMedPubMedCentral

10.

Wang B, Zheng J, Chen Q et al (2020) CLIC4 abrogation promotes epithelial-mesenchymal transition in gastric cancer. Carcinogenesis 41:841–849. https://doi.org/10.1093/carcin/bgz156CrossRefPubMed

11.

Sasaki K, Natsugoe S, Ishigami S et al (2009) Significance of twist expression and its association with E-cadherin in esophageal squamous cell carcinoma. J Exp Clin Cancer Res 28:158. https://doi.org/10.1186/1756-9966-28-158CrossRefPubMedPubMedCentral

12.

Gomes IP, Bastos VC, Guimarães LM, Gomes CC (2023) The molecular basis of odontogenic cysts and tumours. J Oral Pathol Med 52:351–356. https://doi.org/10.1111/jop.13401CrossRefPubMed

13.

Lima FJ, Lopes MLDDS, Barros CCDS et al (2020) Modification in CLIC4 expression is Associated with P53, TGF-β, TNF-α and myofibroblasts in Lip Carcinogenesis. Braz Dent J 31:290–297. https://doi.org/10.1590/0103-6440202003104CrossRefPubMed

14.

Xerez MC, Barros CCS, Queiroz SI et al (2023) The stromal immunoexpression of CLIC4 may be related to the difference in the biological behavior between oral squamous cell carcinoma and oral verrucous carcinoma. Med Oral Patol Oral Cir Bucal 28:e418–e424. https://doi.org/10.4317/medoral.25842CrossRefPubMedPubMedCentral

15.

Suh KS, Crutchley JM, Koochek A et al (2007) Reciprocal modifications of CLIC4 in Tumor Epithelium and Stroma Mark Malignant progression of multiple human cancers. Clin Cancer Res 13:121–131. https://doi.org/10.1158/1078-0432.CCR-06-1562CrossRefPubMed

16.

Suh KS, Mutoh M, Mutoh T et al (2007) CLIC4 mediates and is required for Ca2⁺-induced keratinocyte differentiation. J Cell Sci 120:2631–2640. https://doi.org/10.1242/jcs.002741CrossRefPubMed

17.

Nakazawa M, Kyprianou N (2017) Epithelial-mesenchymal-transition regulators in prostate cancer: androgens and beyond. J Steroid Biochem Mol Biol 166:84–90. https://doi.org/10.1016/j.jsbmb.2016.05.007CrossRefPubMed

18.

Zang C, Liu X, Li B et al (2017) IL-6/STAT3/TWIST inhibition reverses ionizing radiation-induced EMT and radioresistance in esophageal squamous carcinoma. Oncotarget 8:11228–11238. https://doi.org/10.18632/oncotarget.14495CrossRefPubMedPubMedCentral

19.

Dongre A, Weinberg RA (2019) New insights into the mechanisms of epithelial-mesenchymal transition and implications for cancer. Nat Rev Mol Cell Biol 20:69–84. https://doi.org/10.1038/s41580-018-0080-4CrossRefPubMed

20.

Corso G, Figueiredo J, De Angelis SP et al (2020) E-cadherin deregulation in breast cancer. J Cell Mol Med 24:5930–5936. https://doi.org/10.1111/jcmm.15140CrossRefPubMedPubMedCentral

21.

Kaszak I, Witkowska-Piłaszewicz O, Niewiadomska Z et al (2020) Role of cadherins in Cancer-A Review. Int J Mol Sci 21:7624. https://doi.org/10.3390/ijms21207624CrossRefPubMedPubMedCentral

22.

Hao F, Liu J, Zhong M, Wang J, Liu J (2018) Expression of E-cadherin, vimentin and β-catenin in ameloblastoma and association with clinicopathological characteristics of ameloblastoma. Int J Clin Exp Pathol 11:199–207PubMedPubMedCentral

23.

Zhong WQ, Chen G, Zhang W et al (2015) Epithelial-mesenchymal transition in keratocystic odontogenic tumor: possible role in locally aggressive behavior. Biomed Res Int 2015:168089. https://doi.org/10.1155/2015/168089

24.

Zhang J, Wang Y, Fan C et al (2019) Interleukin-8/β-catenin mediates epithelial-mesenchymal transition in ameloblastoma. Oral Dis 25:1964–1971. https://doi.org/10.1111/odi.13173CrossRefPubMed

25.

Barnts K, Feng JQ, Qin C, Zhang H, Cheng YL (2022) Adenomatoid odontogenic tumor: evidence for a mixed odontogenic tumor. Oral Surg Oral Med Oral Pathol Oral Radiol 133:675–683. https://doi.org/10.1016/j.oooo.2021.11.005CrossRefPubMed

26.

Suh KS, Malik M, Shukla A, Yuspa SH (2007) CLIC4, skin homeostasis and cutaneous cancer: surprising connections. Mol Carcinog 46:599–604. https://doi.org/10.1002/mc.20324CrossRefPubMed

27.

Syamala D, Suresh R, Janardhanan M et al (2016) Immunohistochemical evaluation of myofibroblasts in odontogenic cysts and tumors: a comparative study. J Oral Maxillofac Pathol 20:208–213. https://doi.org/10.4103/0973-029X.185898CrossRefPubMedPubMedCentral

Titel: CLIC4 Function in the Epithelial-Mesenchymal Transition of Epithelial Odontogenic Lesions
verfasst von: Mariana Carvalho Xerez
Caio César da Silva Barros
Maurília Raquel de Souto Medeiros
Rodrigo Porpino Mafra
Hévio Freitas de Lucena
Éricka Janine Dantas da Silveira
Antonio de Lisboa Lopes Costa
Publikationsdatum: 01.12.2024
Verlag: Springer US
Erschienen in: Head and Neck Pathology / Ausgabe 1/2024
Elektronische ISSN: 1936-0568
DOI: https://doi.org/10.1007/s12105-024-01646-1

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

CLIC4 Function in the Epithelial-Mesenchymal Transition of Epithelial Odontogenic Lesions

Abstract

Background

Methods

Results

Conclusions

Neu im Fachgebiet Pathologie

Assistierter Suizid durch Infusion von Thiopental

Molekularpathologische Untersuchungen im Wandel der Zeit

Vergleichende Pathologie in der onkologischen Forschung

Gastrointestinale Stromatumoren

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Abstract

Background

Methods

Results

Conclusions

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 1/2024

Unraveling the Genetic Web: H-Ras Expression and Mutation in Oral Squamous Cell Carcinoma—A Systematic Review

Author Correction: Top IHC/ISH Hacks for and Molecular Surrogates of Poorly Differentiated Sinonasal Small Round Cell Tumors

An Evaluation of High-Risk HPV in Squamous Cell Carcinomas of the Lip in a South African Cohort

Chronic Lymphocytic Thyroiditis with Oncocytic Metaplasia Influences PD-L1 Expression in Papillary Thyroid Carcinoma

SMARCB1-Deficient Skull Base Chondrosarcoma with 12p Duplication Presenting as Somatic-Type Malignancy Arising from Metastatic Seminoma

Extramammary Paget Disease of Oral Mucosa: Case Report with Literature Review

Neu im Fachgebiet Pathologie

Assistierter Suizid durch Infusion von Thiopental

Molekularpathologische Untersuchungen im Wandel der Zeit

Vergleichende Pathologie in der onkologischen Forschung

Gastrointestinale Stromatumoren