Skip to main content

Advertisement

Log in

Oct-4 and CD44 in epithelial stem cells like of benign odontogenic lesions

  • Original Paper
  • Published:
Histochemistry and Cell Biology Aims and scope Submit manuscript

Abstract

Benign epithelial odontogenic lesions are great clinical importance entities that develop in the jaws from the tissues that form teeth. It has been shown that benign and malignant tumors are present in a large number of tumor stem cells, which has great implications in the development of these lesions. Oct-4 and CD44 have been demonstrated as important markers for tumoral stem cells. The aim of this study was investigate the presence of stem cell markers Oct-4 and CD44 in benign epithelial odontogenic lesions. Twenty odontogenic keratocysts (OKC), 20 ameloblastomas (AMB) of the solid/multicystic type and 20 adenomatoid odontogenic tumors (AOT) were retrospectively analyzed for immunohistochemical detection of Oct-4 and CD44 in their epithelial component. All cases were positive for the two markers, with the majority exhibiting a high expression. Analysis of the expression of Oct-4 revealed no statistically significant differences (p = 0.406) between the lesions studied. Regarding CD44, there was a significant difference between the cases of AMB and AOT in relation with OKC, with the latter presenting a greater labelling (p = 0.034). No statistically significant correlation between Oct-4 and CD44 was observed in the lesions. In our findings, the presence of stem cell-like phenotype at various sites of the epithelial component of the odontogenic lesions was identified, suggesting its possible participation in histogenesis and differentiation without, however, exerting influence on the aggressiveness of the lesions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  • Almeida LO, Guimarães DM, Squarize CH, Castilho RM (2016) Profiling the behavior of distinct populations of head and neck cancer stem cells. Cancers (Basel) 8:1

    Article  CAS  Google Scholar 

  • Amaral FR, Mateus GC, Bonisson LA, de Andrade BA, Mesquita RA, Horta MC, de Marigo HA (2016) Cell proliferation and apoptosis in ameloblastomas and keratocystic odontogenic tumors. Braz Dent J 23:91–96

    Article  Google Scholar 

  • Bandyopadhyay A, Nishat R, Behura SS, Panda A, Ramachandra S, Mohiddin G (2017) Cancer stem cell markers, SOX2 and OCT4 in ameloblastoma and keratocystic odontogenic tumor: an immunohistochemical study. Int J Oral Health 9:28–32

    Article  Google Scholar 

  • Banerjee A, Kamath VV, Sundaram L, Krishnamurthy SS (2016) OCT4 and SOX2 are reliable markers in detecting stem cells in odontogenic lesions. J Orofac Sci 8:16–21

    Article  CAS  Google Scholar 

  • Bilodeau EA, Collins BM (2017) Odontogenic cysts and neoplasms. Surg Pathol Clin 10:177–222

    Article  PubMed  Google Scholar 

  • Bilodeau EA, Acquafondata M, Barnes EL, Seethala RR (2015) A comparative analysis of LEF-1 in odontogenic and salivary tumors. Hum Pathol 46:255–259

    Article  CAS  PubMed  Google Scholar 

  • Chang JYF, Wang C, Jin CL, Yang C, Huang Y, Liu J, McKeehan WL, D’Souza RN, Wang F (2013) Self-renewal and multilineage differentiation of mouse dental epithelial stem cells. Stem Cell Res 11:990–1002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • de Vicente JC, Torre-Iturraspe A, Gutiérrez AM, Lequerica-Fernández P (2010) Immunohistochemical comparative study of the odontogenic keratocysts and other odontogenic lesions. Med Oral Patol Oral Cir Bucal 15:e709

    Article  PubMed  Google Scholar 

  • Fu TY, Hsieh IC, Cheng JT, Tsai MH, Hou YY, Lee JH, Liou HH, Huang SF, Chen HC, Yen LM, Tseng HH, Ger LP (2016) Association of OCT4, SOX2, and NANOG expression with oral squamous cell carcinoma progression. J Oral Pathol Med 45:89–95

    Article  CAS  PubMed  Google Scholar 

  • Ge N, Lin HX, Xiao XS, Guo L, Xu HM, Wang X, Jin T, Cai XY, Liang Y, Hu WH, Kang T (2010) Prognostic significance of Oct4 and Sox2 expression in hypopharyngeal squamous cell carcinoma. J Transl Med 8:94

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Harada H, Mitsuyasu T, Toyono T, Toyoshima K (2002) Epithelial stem cells in teeth. Odontology 90:1

    Article  PubMed  Google Scholar 

  • Hassiotou F, Hepworth AR, Beltran AS, Mathews MM, Stuebe AM, Hartmann PE, Filgueira L, Blancafort P (2013) Expression of the pluripotency transcription factor OCT4 in the normal and aberrant mammary gland. Front Oncol 3:79

    Article  PubMed  PubMed Central  Google Scholar 

  • Heikinheimo K, Kurppa KJ, Laiho A, Peltonen S, Berdal A, Bouattour A, Ruhin B, Catón J, Thesleff I, Leivo I, Morgan PR et al (2015) Early dental epithelial transcription factors distinguish ameloblastoma from keratocystic odontogenic tumor. J Dent Res 94:101–111

    Article  CAS  PubMed  Google Scholar 

  • Huang CF, Xu XR, Wu TF, Sun ZJ, Zhang WF (2014) Correlation of ALDH1, CD44, OCT4 and SOX2 in tongue squamous cell carcinoma and their association with disease progression and prognosis. J Oral Pathol Med 43:492–498

    Article  CAS  PubMed  Google Scholar 

  • Islam F, Qiao B, Smith RA, Gopalan V, Lam AK (2015) Cancer stem cell: fundamental experimental pathological concepts and updates. Exp Mol Pathol 98:184–191

    Article  CAS  PubMed  Google Scholar 

  • Jordan AR, Racine RR, Hennig MJ, Lokeshwar VB (2015) The role of CD44 in disease pathophysiology and targeted treatment. Front Immunol 21:182

    Google Scholar 

  • Juuri E, Isaksson S, Jussila M, Heikinheimo K, Thesleff I (2013a) Expression of the stem cell marker, SOX2, in ameloblastoma and dental epithelium. Eur J Oral Sci 121:509–516

    Article  CAS  PubMed  Google Scholar 

  • Juuri E, Jussila M, Seidel K, Holmes S, Wu P, Richman J, Heikinheimo K, Chuong CM, Arnold K, Hochedlinger K, Klein O, Michon F, Thesleff I (2013b) Sox2 marks epithelial competence to generate teeth in mammals and reptiles. Development 140:1424–1432

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kero D, Novakovic J, Vukojevic K, Petricevic J, Kalibovic Govorko D, Biocina-Lukenda D, Saraga-Babic M (2014) Expression of Ki-67, Oct-4, γ-tubulin and α-tubulin in human tooth development. Arch Oral Biol 59:1119–1129

    Article  CAS  PubMed  Google Scholar 

  • Lei Y, Jaradat JM, Owosho A, Adebiyi KE, Lybrand KS, Neville BW, Müller S, Bilodeau EA (2014) Evaluation of SOX2 as a potential marker for ameloblastic carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol 117:608–616

    Article  PubMed  Google Scholar 

  • Li XP, Zhang XW, Zheng LZ, Guo WJ (2015) Expression of CD44 in pancreatic cancer and its significance. Int J Clin Exp Pathol 8:6724–6731

    CAS  PubMed  PubMed Central  Google Scholar 

  • Mamabolo M, Noffke C, Raubenheimer E (2011) Odontogenic tumours manifesting in the first two decades of life in a rural African population sample: a 26 year retrospective analysis. Dentomaxillofac Radiol 40:331–337

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mendenhall WM, Werning JW, Fernandes R, Malyapa RS, Mendenhall NP (2007) Ameloblastoma. Am J Clin Oncol 30:645–648

    Article  PubMed  Google Scholar 

  • Mohamed A, Singh AS, Raubenheimer EJ, Bouckaert MM (2010) Adenomatoid odontogenic tumour: review of the literature and an analysis of 33 cases from South Africa. Int J Oral Maxillofac Surg 39:843–846

    Article  CAS  PubMed  Google Scholar 

  • Peng Z, Liu L, Wei X, Ling J (2014) Expression of Oct-4, SOX-2, and MYC in dental papilla cells and dental follicle cells during in-vivo tooth development and in-vitro co-culture. Eur J Oral Sci 122:251–258

    Article  CAS  PubMed  Google Scholar 

  • Philipsen HP, Reichart PA, Siar CH, Ng KH, Lau SH, Zhang X, Dhanuthai K, Swasdison S, Jainkittivong A, Meer S, Jivan V, Altini M, Hazarey V, Ogawa I, Takata T, Taylor AA, Godoy H, Delgado WA, Carlos-Bregni R, Macias JF, Matsuzaka K, Sato D, Vargas PA, Adebayo ET (2007) An updated clinical and epidemiological profile of the adenomatoid odontogenic tumour: a collaborative retrospective study. J Oral Pathol Med 36:383–393

    Article  PubMed  Google Scholar 

  • Puthiyaveetil JSV, Kota K, Chakkarayan R, Chakkarayan J, Thodiyil AK (2016) Epithelial-mesenchymal interactions in tooth development and the significant role of growth factors and genes with emphasis on mesenchyme—a review. J Clin Diagn Res 10(9):ZE05–ZE09

    PubMed  PubMed Central  Google Scholar 

  • Ramanathan A, Srijaya TC, Sukumaran P, Zain RB, Abu Kasim NH (2018) Homeobox genes and tooth development: understanding the biological pathways and applications in regenerative dental science. Arch Oral Biol 85:23–39

    Article  CAS  PubMed  Google Scholar 

  • Salehinejad J, Saghafi S, Sharifi N, Zare-Mahmoodabadi R, Saghravanian N, Ghazi N, Shakeri MT (2012) Evaluation of osteopontin and CD44v6 expression in odontogenic cystic lesions by immunohistochemistry. Pathol Res Pract 208:410–414

    Article  CAS  PubMed  Google Scholar 

  • Sathi GA, Tamamura R, Tsujigiwa H, Katase N, Lefeuvre M, Siar CH, Matsuda H, Nagatsuka H (2012) Analysis of immunoexpression of common cancer stem cell markers in ameloblastoma. Exp Ther Med 3:397–402

    Article  PubMed  Google Scholar 

  • Sawant S, Gokulan R, Dongre H, Vaidya M, Chaukar D, Prabhash K, Ingle A, Joshi S, Dange P, Joshi S, Singh AK, Makani V, Sharma S, Jeyaram A, Kane S, D’Cruz A (2016) Prognostic role of Oct4, CD44 and c-Myc in radio-chemo-resistant oral cancer patients and their tumourigenic potential in immunodeficient mice. Clin Oral Investig 20:43–56

    Article  PubMed  Google Scholar 

  • Senbanjo LT, Chellaiah MA (2017) CD44: a multifunctional cell surface adhesion receptor is a regulator of progression and metastasis of cancer cells. Front Cell Dev Biol 5:18

    Article  PubMed  PubMed Central  Google Scholar 

  • Sung B, Do HJ, Park SW, Huh SH, Oh JH, Chung HJ, Kang MJ, Kim JH, Kim NH, Kim JH (2012) Regulation of OCT4 gene expression by liver receptor homolog-1 in human embryonic carcinoma cells. Biochem Biophys Res Commun 427:315–320

    Article  CAS  PubMed  Google Scholar 

  • Suryadeva S, Khan MB (2015) Role of homeobox genes in tooth morphogenesis: a review. J Clin Diagn Res 9(2):ZE09–ZE12

    CAS  PubMed  PubMed Central  Google Scholar 

  • Takaishi S, Okumura T, Tu S, Wang SS, Shibata W, Vigneshwaran R, Gordon SA, Shimada Y, Wang TC (2009) Identification of gastric cancer stem cells using the cell surface marker CD44. Stem Cells 27:1006–1020

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tawfik MA, Zyada MM (2010) Odontogenic tumors in Dakahlia, Egypt: analysis of 82 cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 109:67–73

    Article  Google Scholar 

  • Thosaporn W, Iamaroon A, Pongsiriwet S, Ng KH (2004) A comparative study of epithelial cell proliferation between the odontogenic keratocyst, orthokeratinized odontogenic cyst, dentigerous cyst, and ameloblastoma. Oral Dis 10:22–26

    Article  CAS  PubMed  Google Scholar 

  • Tsai LL, Hu FW, Lee SS, Yu CH, Yu CC, Chang YC (2014) Oct4 mediates tumor initiating properties in oral squamous cell carcinomas through the regulation of epithelial-mesenchymal transition. PLoS One 9:e87207

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang YP, Liu BY (2009a) Expression of osteopontin and its receptors in ameloblastoma. Oral Oncol 45:538–542

    Article  CAS  PubMed  Google Scholar 

  • Wang YP, Liu BY (2009b) High expression of osteopontin and CD44v6 in odontogenic keratocysts. J Formos Med Assoc 108:286–292

    Article  CAS  PubMed  Google Scholar 

  • Wu G, Schöler HR (2014) Role of Oct4 in the early embryo development. Cell Regen (Lond) 3:7

    Google Scholar 

  • Yu S, Cai X, Wu C, Wu L, Wang Y, Liu Y, Yu Z, Qin S, Ma F, Thiery JP, Chen L (2015) Adhesion glycoprotein CD44 functions as an upstream regulator of a network connecting ERK, AKT and Hippo-YAP pathways in cancer progression. Oncotarget 6:2951–2965

    PubMed  Google Scholar 

  • Zhang X, Hua R, Wang X, Huang M, Gan L, Wu Z, Zhang J, Wang H, Cheng Y, Li J, Guo W (2016) Identification of stem-like cells and clinical significance of candidate stem cell markers in gastric cancer. Oncotarget 7:9815–9831

    PubMed  PubMed Central  Google Scholar 

Download references

Funding

This study was funded by National Council for Scientific and Technological Development (CNPq) (Grant no. 307539/2010-5)—Lélia Batista de Souza.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Lélia Batista de Souza.

Ethics declarations

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Monroy, E.A.C., de Andrade Santos, P.P., de Sousa Lopes, M.L.D. et al. Oct-4 and CD44 in epithelial stem cells like of benign odontogenic lesions. Histochem Cell Biol 150, 371–377 (2018). https://doi.org/10.1007/s00418-018-1692-7

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00418-018-1692-7

Keywords

Navigation