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Snail promotes an invasive phenotype in lung carcinoma

Heta Merikallio12*, Taina Turpeenniemi-Hujanen3, Paavo Pääkkö4, Riitta Mäkitaro1, Kaarteenaho Riitta12, Sirpa Salo5, Tuula Salo56, Terttu Harju12 and Ylermi Soini7

Author Affiliations

1 Department of Internal Medicine, Respiratory Research Unit, University of Oulu and Oulu University Hospital, Oulu, Finland

2 Clinical Research Center, Oulu University Hospital, Oulu, Finland

3 Department of Oncology and Haematolgy, University Hospital of Oulu, University of Oulu, Oulu, Finland

4 Department Pathology, University Hospital of Oulu, Oulu, Finland

5 Oulu Center for Cell-Matrix Research, Institute of Dentistry, University of Oulu, Oulu, Finland

6 Institute of Dentistry, University of Helsinki, Helsinki, Finland

7 Department of Pathology and Forensic Medicine, University of Eastern Finland, Kuopio and Cancer Center of Eastern Finland, Kuopio, Finland

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Respiratory Research 2012, 13:104  doi:10.1186/1465-9921-13-104

Published: 17 November 2012

Abstract

Background

Snail is a transcriptional factor which is known to influence the epitheliomesenchymal transition (EMT) by regulating adhesion proteins such as E-cadherin and claudins as well as matrix metalloproteases (MMP).

Methods

To evaluate the functional importance of snail, a transciptional factor involved in EMT in lung tumors, we investigated its expression in a large set of lung carcinomas by immunohistochemistry. Expression of snail and effects of snail knockdown was studied in cell lines.

Results

Nuclear snail expression was seen in 21% of cases this being strongest in small cell lung carcinomas (SCLC). There was significantly greater snail expression in SCLC compared to squamous cell or adenocarcinoma. Positive snail expression was associated with poor survival in the whole material and separately in squamous cell and adenocarcinomas. In Cox regression analysis, snail expression showed an independent prognostic value in all of these groups. In several cell lines knockdown of snail reduced invasion in both matrigel assay and in the myoma tissue model for invasion. The influence of snail knockdown on claudin expression was cell type specific. Snail knockdown in these cell lines modified the expression of MMP2 and MMP9 but did not influence the activation of these MMPs to any significant degree.

Conclusions

The results show that snail plays an important role in the invasive characteristics of lung carcinoma influencing the survival of the patients. Snail knockdown might thus be one option for targeted molecular therapy in lung cancer. Snail knockdown influenced the expression of claudins individually in a cell-line dependent manner but did not influence MMP expressions or activations to any significant degree.

Keywords:
Lung; Carcinoma; Snail; Claudin; MMP