Skip to main content

Advertisement

SpringerLink
Log in

Epithelial to mesenchymal transition in cutaneous squamous cell carcinoma is correlated with COX-2 expression but not with the presence of stromal macrophages or CD10-expressing cells

  • Original Article
  • Published:
Virchows Archiv Aims and scope Submit manuscript

Abstract

Epithelial to mesenchymal transition (EMT) is an intricate process by which epithelial cells loose epithelial characteristics and acquire a mesenchymal-like phenotype. EMT and cyclooxygenase 2 (COX-2) expression are related to tumor invasion and metastasis. The tumor microenvironment plays a major role in tumor progression and the induction of EMT. Here, we investigated the relationship between EMT and COX-2 expression as well as tumor-associated macrophages (TAM) and CD10-positive stromal cells during the development of cutaneous squamous neoplastic lesion. We performed immunohistochemical staining for vimentin, E-cadherin, β-catenin, COX-2, CD68, and CD10 in 41 cases of squamous cell cancers (SCC), 20 of Bowen’s disease, 30 of actinic keratosis, and 30 samples of normal skin. SCC cells showed significantly increased vimentin expression and reduced expression of membranous E-cadherin and β-catenin compared with cells in precursor lesions and in normal skin. COX-2 expression was also markedly increased in SCC cells. E-cadherin expression was positively correlated with β-catenin expression and inversely correlated with COX-2 expression in SCC cells. The number of TAM and CD10-positive stromal cells increased from the normal skin to precursor lesions and SCC cells. The number of TAM and of CD10-positive stromal cells did not correlate with the expression of E-cadherin, β-catenin, COX-2, and vimentin in SCC cells. We suggest that cutaneous SCC cells show EMT, which appears to be correlated with COX-2 expression but not with stromal CD10 expression and TAM.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Vleminckx K, Kemler R (1999) Cadherins and tissue formation: integrating adhesion and signaling. Bioessays 21:211–220

    Article  PubMed  CAS  Google Scholar 

  2. Thiery JP (2002) Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer 2:442–454

    Article  PubMed  CAS  Google Scholar 

  3. Hirohashi S (1998) Inactivation of the E-cadherin-mediated cell adhesion system in human cancer. Am J Pathol 153:333–339

    Article  PubMed  CAS  Google Scholar 

  4. Guarino M, Rubino B, Ballabio G (2007) The role of epithelial-mesenchymal transition in cancer pathology. Pathology 39:305–318

    Article  PubMed  CAS  Google Scholar 

  5. Papadavid E, Pignatelli M, Zakynthinos S, Krausz T, Chu AC (2002) Abnormal immunoreactivity of the E-cadherin/catenin (alpha-, beta-, and gamma-) complex in premalignant and malignant non-melanocytic skin tumours. J Pathol 196:154–162

    Article  PubMed  CAS  Google Scholar 

  6. Czech W, Krutmann J, Herrejnetcht K, Schopf E, Kapp A (1993) Human cell adhesion molecule uvomorulin is differentially expressed in various skin tumors. J Cutan Pathol 20:168–172

    Article  PubMed  CAS  Google Scholar 

  7. Lyakhovitsky A, Barzilai A, Fogel M, Trau H, Huszar M (2004) Expression of e-cadherin and beta-catenin in cutaneous squamous cell carcinoma and its precursors. Am J Dermatopathol 26:372–378

    Article  PubMed  Google Scholar 

  8. Barth AI, Näthke IS, Nelson WJ (1997) Cadherins, catenins and APC protein: interplay between cytoskeletal complexes and signaling pathways. Curr Opin Cell Biol 9:683–690

    Article  PubMed  CAS  Google Scholar 

  9. Brembeck FH, Rosário M, Birchmeier W (2006) Balancing cell adhesion and Wnt signaling, the key role of beta-catenin. Curr Opin Genet Dev 16:51–59

    Article  PubMed  CAS  Google Scholar 

  10. Brasanac D, Boricic I, Todorovic V, Tomanovic N, Radojevic S (2005) Cyclin A and beta-catenin expression in actinic keratosis, Bowen’s disease and invasive squamous cell carcinoma of the skin. Br J Dermatol 153:1166–1175

    Article  PubMed  CAS  Google Scholar 

  11. Tsujii M, DuBois RN (1995) Alterations in cellular adhesion and apoptosis in epithelial cells overexpressing prostaglandin endoperoxide synthase 2. Cell 83:493–501

    Article  PubMed  CAS  Google Scholar 

  12. Tsujii M, Kawano S, DuBois RN (1997) Cyclooxyenase-2 expression in human colon cancer cells increases metastatic potential. Proc Natl Acad Sci U S A 94:3336–3340

    Article  PubMed  CAS  Google Scholar 

  13. Nijsten T, Colpaert CG, Vermeulen PB, Harris AL, Van Marck E, Lambert J (2004) Cyclooxygenase-2 expression and angiogenesis in squamous cell carcinoma of the skin and its precursors: a paired immunohistochemical study of 35 cases. Br J Dermatol 151:837–845

    Article  PubMed  CAS  Google Scholar 

  14. Muller-Decker K, Reinerth G, Krieg P et al (1999) Prostaglandin-H synthase isozyme expression in normal and neoplastic skin. Int J Cancer 82:648–656

    Article  PubMed  CAS  Google Scholar 

  15. Kagoura M, Toyoda M, Matsui C et al (2001) Immunohistochemical expression of cyclooxygenase-2 in skin cancers. J Cutan Pathol 28:298–302

    Article  PubMed  CAS  Google Scholar 

  16. Denkert C, Kobel M, Berger S et al (2001) Expression of cyclooxygenase 2 in human malignant melanoma. Cancer Res 61:303–308

    PubMed  CAS  Google Scholar 

  17. Brouxhon S, Kyrkanides S, O’Banion MK et al (2007) Sequential down-regulation of E-cadherin with squamous cell carcinoma progression: loss of E-cadherin via a prostaglandin E2-EP2-dependent posttranslational mechanism. Cancer Res 67:7654–7664

    Article  PubMed  CAS  Google Scholar 

  18. Dohadwala M, Yang SC, Luo J et al (2006) Cyclooxygenase-2-dependent regulation of E-cadherin: prostaglandin E2 induces transcriptional repressors ZEB1 and snail in non-small cell lung cancer. Cancer Res 66:5338–5345

    Article  PubMed  CAS  Google Scholar 

  19. Jing Y, Han Z, Zhang S, Liu Y, Wei L (2011) Epithelial-mesenchymal transition in tumor microenvironment. Cell Biosci 1:29

    Article  PubMed  CAS  Google Scholar 

  20. Ungefroren H, Sebens S, Seidl D, Lehnert H, Hass R (2011) Interaction of tumor cells with the microenvironment. Cell Commun Signal 9:18

    Article  PubMed  CAS  Google Scholar 

  21. Chen JJ, Lin YC, Yao PL et al (2005) Tumor associated macrophages: the double-edged sword in cancer progression. J Clin Oncol 23:953–964

    Article  PubMed  CAS  Google Scholar 

  22. Lewis CE, Pollard JW (2006) Distinct role of macrophages in different tumor microenvironments. Cancer Res 66:605–612

    Article  PubMed  CAS  Google Scholar 

  23. Dong R, Wang Q, He XL, Chu YK, Lu JG, Ma QJ (2007) Role of nuclear factor kappa B and reactive oxygen species in the tumor necrosis factor-alpha induced epithelial-mesenchymal transition of MCF-7 cells. Braz J Med Biol Res 40:1071–1078

    Article  PubMed  CAS  Google Scholar 

  24. Takahara M, Chen S, Kido M et al (2009) Stromal CD10 expression, as well as increased dermal macrophages and decreased Langerhans cells, are associated with malignant transformation of keratinocytes. J Cutan Pathol 36:668–674

    Article  PubMed  Google Scholar 

  25. Albrecht M, Gillen S, Wilhelm B et al (2002) Expression, localization and activity of neutral endopeptidase in cultured cells of benign prostatic hyperplasia and prostate cancer. J Urol 168:336–342

    Article  PubMed  CAS  Google Scholar 

  26. Iwaya K, Ogawa H, Izumi M et al (2002) Stromal expression of CD10 in invasive breast carcinoma: a new predictor of clinical outcome. Virchows Arch 440:589–593

    Article  PubMed  CAS  Google Scholar 

  27. Kesse-Adu R, Shousha S (2004) Myoepithelial markers are expressed in at least 29% of oestrogen receptor negative invasive breast carcinoma. Mod Pathol 17:646–652

    Article  PubMed  CAS  Google Scholar 

  28. Ogawa H, Iwaya K, Izumi M et al (2002) Expression of CD10 by stromal cells during colorectal tumor development. Hum Pathol 33:806–811

    Article  PubMed  Google Scholar 

  29. Jang TJ, Cha WH, Lee KS (2010) Reciprocal correlation between the expression of cyclooxygenase-2 and E-cadherin in human bladder transitional cell carcinomas. Virchows Arch 457:319–328

    Article  PubMed  CAS  Google Scholar 

  30. Fuller LC, Allen MH, Montesu M, Barker JN, MacDonald DM (1996) Expression of E-cadherin in human epidermal non-melanoma cutaneous tumours. Br J Dermatol 134:28–32

    Article  PubMed  CAS  Google Scholar 

  31. Park SH, Cheung LW, Wong AS, Leung PC (2008) Estrogen regulates Snail and Slug in the down-regulation of E-cadherin and induces metastatic potential of ovarian cancer cells through estrogen receptor alpha. Mol Endocrinol 22:2085–2098

    Article  PubMed  CAS  Google Scholar 

  32. Peinado H, Portillo F, Cano A (2004) Transcriptional regulation of cadherins during development and carcinogenesis. Int J Dev Biol 48:365–375

    Article  PubMed  CAS  Google Scholar 

  33. Jang TJ (2009) Cyclooxgenase-2 expression is related to the epithelial-to-mesenchymal transition in human colon cancers. Yon Med J 50:818–824

    Article  CAS  Google Scholar 

  34. Mann JR, Backlund MG, Buchanan FG et al (2006) Repression of prostaglandin dehydrogenase by epidermal growth factor and snail increases prostaglandin E2 and promotes cancer progression. Cancer Res 66:6649–6656

    Article  PubMed  CAS  Google Scholar 

  35. Fukumaru K, Yoshii N, Kanzaki T, Kanekura T (2007) Immunohistochemical comparison of beta-catenin expression by human normal epidermis and epidermal tumors. J Dermatol 34:746–753

    Article  PubMed  CAS  Google Scholar 

  36. Moreno-Bueno G, Gamallo C, Perez-Gallego L et al (2001) β-catenin expression in pilomatrixomas. Relationship with β-catenin gene mutations and comparison with β-catenin expression in normal hair follicles. Br J Dermatol 145:576–581

    Article  PubMed  CAS  Google Scholar 

  37. Doglioni C, Piccinin S, Demontis S et al (2003) Alterations of β-catenin pathway in non-melanoma skin tumors. Loss of α-ABC nuclear reactivity correlates with the presence of β-catenin gene mutation. Am J Pathol 163:2277–2287

    Article  PubMed  CAS  Google Scholar 

  38. Ruiter D, Bogenrieder T, Elder D, Herlyn M (2002) Melanoma-stroma interactions: structural and functional aspects. Lancet Oncol 3:35–43

    Article  PubMed  CAS  Google Scholar 

  39. Olerud JE, Usui ML, Seckin D et al (1999) Neutral endopeptidase expression and distribution in human skin and wounds. J Invest Dermatol 112:873–881

    Article  PubMed  CAS  Google Scholar 

  40. Basset P, Wolf C, Rouyer N, Bellocq JP, Rio MC, Chambon P (1994) Stromelysin-3 in stromal tissue as a control factor in breast cancer behavior. Cancer 74:1045–1049

    Article  PubMed  CAS  Google Scholar 

  41. Sica A, Larghi P, Mancino A et al (2008) Macrophage polarization in tumour progression. Sem Cancer Biol 18:349–355

    Article  CAS  Google Scholar 

  42. Kalluri R, Weinberg RA (2009) The basics of epithelial-mesenchymal transition. J Clin Invest 119:1420–1428

    Article  PubMed  CAS  Google Scholar 

  43. Tjiu JW, Chen JS, Shun CT (2009) Tumor-associated macrophage-induced invasion and angiogenesis of human basal cell carcinoma cells by cyclooxygenase-2 induction. J Invest Dermatol 129:1016–1025

    Article  PubMed  CAS  Google Scholar 

Download references

Conflict of interest

I declare that I have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Pathology, Dongguk University College of Medicine, Sukjang-dong 707, Gyeongju, Gyeongbuk, 780-714, South Korea

    Tae Jung Jang

Authors
  1. Tae Jung Jang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tae Jung Jang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jang, T.J. Epithelial to mesenchymal transition in cutaneous squamous cell carcinoma is correlated with COX-2 expression but not with the presence of stromal macrophages or CD10-expressing cells. Virchows Arch 460, 481–487 (2012). https://doi.org/10.1007/s00428-012-1227-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00428-012-1227-x

Keywords

Search

Navigation