Loss of E-cadherin and Acquisition of Vimentin in Epithelial-Mesenchymal Transition are Noble Indicators of Uterine Cervix Cancer Progression
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Background: Epithelial-mesenchymal transition (EMT) has been known to play a key role in the stromal invasion of carcinoma in situ (CIS) lesion. Loss of E-cadherin and acquisition of vimentin are two critical steps in EMT, that are induced by Snail-1 upregulation associated with overexpression of epidermal growth factor receptor (EGFR). However, roles of EMT-related proteins in human cervical tissues have not been fully elucidated. In this study, we investigated the immunoexpressions of EMT-related proteins in CIS, microinvasive squamous cell carcinoma (SCC), and invasive SCC to demonstrate their key roles in tumor progression. Methods: Eighty one CIS, 17 microinvasive, and 21 invasive SCC cases were immunostained with primary antibodies for Snail-1, EGFR, E-cadherin, and vimentin on paraffin-embedded tissue microarray blocks. Results: EGFR and Snail-1 proteins were highly expressed but the levels were not significantly different between the three groups. However, loss of E-cadherin and acquisition of vimentin were proven to occur significantly higher in microinvasive and invasive SCC cases than in CIS. Conclusions: E-cadherin and vimentin were found to be two useful indicators of EMT in evaluating stromal invasion of CIS. However, it was not demonstrated for Snail-1 and EGFR proteins to play any key role in the progression of cervix cancer.
Abstract
Background: Epithelial-mesenchymal transition (EMT) has been known to play a key role in the stromal invasion of carcinoma in situ (CIS) lesion. Loss of E-cadherin and acquisition of vimentin are two critical steps in EMT, that are induced by Snail-1 upregulation associated with overexpression of epidermal growth factor receptor (EGFR). However, roles of EMT-related proteins in human cervical tissues have not been fully elucidated. In this study, we investigated the immunoexpressions of EMT-related proteins in CIS, microinvasive squamous cell carcinoma (SCC), and invasive SCC to demonstrate their key roles in tumor progression. Methods: Eighty one CIS, 17 microinvasive, and 21 invasive SCC cases were immunostained with primary antibodies for Snail-1, EGFR, E-cadherin, and vimentin on paraffin-embedded tissue microarray blocks. Results: EGFR and Snail-1 proteins were highly expressed but the levels were not significantly different between the three groups. However, loss of E-cadherin and acquisition of vimentin were proven to occur significantly higher in microinvasive and invasive SCC cases than in CIS. Conclusions: E-cadherin and vimentin were found to be two useful indicators of EMT in evaluating stromal invasion of CIS. However, it was not demonstrated for Snail-1 and EGFR proteins to play any key role in the progression of cervix cancer.
참고문헌 (20)
- Lee MY, "Epithelial-mesenchymal transition in cervical cancer: correlation with tumor progression, epidermal growth factor receptor overexpression, and snail up-regulation", Clin Cancer Res, 14, pp.4743~4750 (2008)
- Pignatelli M., "E-cadherin: a biological marker of tumour differentiation", J Pathol, 171, pp.81~82 (1993)
- Frixen UH, "E-cadherin-mediated cell-cell adhesion prevents invasiveness of human carcinoma cells", J Cell Biol, 113, pp.173~185 (1991)
- Yokoyama K, "Reverse correlation of E-cadherin and snail expression in oral squamous cell carcinoma cells in vitro", Oral Oncol, 37, pp.65~71 (2001)
- Batlle E, "The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells", Nat Cell Biol, 2, pp.84~89 (2000)
- Kristensen GB, "Evaluation of the prognostic significance of cathepsin D, epidermal growth factor receptor, and c-erbB-2 in early cervical squamous cell carcinoma: an immunohistochemical study", Cancer, 78, pp.433~440 (1996)
- Soonthornthum T, "Epidermal growth factor receptor as a biomarker for cervical cancer", Ann Oncol, 22, pp.2166~2178 (2011)
- Murakami A, "Relationship between decreased expression of squamous cell carcinoma antigen 2 and E-cadherin in primary cervical cancer lesions and lymph node metastasis", Oncol Rep, 19, pp.99~104 (2008)
- Zhou BP, "Dual regulation of Snail by GSK-3beta-mediated phosphorylation in control of epithelial-mesenchymaltransition", Nat Cell Biol, 6, pp.931~940 (2004)
- Birchmeier W, "Dominant and recessive genes involved in tumor cell invasion", Curr Opin Cell Biol, 3, pp.832~840 (1991)
- Nieto MA, "The snail superfamily of zinc-finger transcription factors", Nat Rev Mol Cell Biol, 3, pp.155~166 (2002)
- Brustmann H, "Expression of phosphorylated histone H2AX (gamma-H2AX) in normal and neoplastic squamous epithelia of the uterine cervix: an immunohistochemical study with epidermal growth factor receptor", Int J Gynecol Pathol, 30, pp.76~83 (2011)
- Jin H, "Snail is critical for tumor growth and metastasis of ovarian carcinoma", Int J Cancer, 126, pp.2102~2111 (2010)
- Cano A, "The transcription factor snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression", Nat Cell Biol, 2, pp.76~83 (2000)
- Kaplanis K, "E-cadherin expression during progression of squamous intraepithelial lesions in the uterine cervix", Eur J Gynaecol Oncol, 26, pp.608~610 (2005)
- Vessey CJ, "Altered expression and function of E-cadherin in cervical intraepithelial neoplasia and invasive squamous cell carcinoma", J Pathol, 176, pp.151~159 (1995)
- Faleiro-Rodrigues C, "E-cadherin, CD44 and CD44v6 in squamous intraepithelial lesions and invasive carcinomas of the uterine cervix: an immunohistochemical study", Pathobiology, 71, pp.329~336 (2004)
- Kawanishi J, "Loss of E-cadherin-dependent cell-cell adhesion due to mutation of the beta-catenin gene in a human cancer cell line, HSC-39", Mol Cell Biol, 15, pp.1175~1181 (1995)
- Huber AH, "The cadherin cytoplasmic domain is unstructured in the absence of beta-catenin: a possible mechanism for regulating cadherin turnover", J Biol Chem, 276, pp.12301~12309 (2001)
- Chen YT, "Coupling assembly of the E-cadherin", beta-catenin complex to efficient endoplasmic reticulum exit and basal-lateral membrane targeting of E-cadherin in polarized MDCK cells, 1999, pp.144, 687~699