Transcription factors related to epithelial mesenchymal transition in tumor center and margin in invasive lung adenocarcinoma

Int J Clin Exp Pathol. 2014 Jun 15;7(7):4095-103. eCollection 2014.

Abstract

The tumor microenvironment has many roles involving tumor progression, invasion and metastasis. The tumor cells at the tumor border loose epithelial properties and acquire mesenchymal features. This, epithelial-to-mesenchymal transition (EMT) has been suggested to be an important process for tissue and lymphovascular invasion. Pulmonary tissue samples from 15 patients with primary adenocarcinoma were evaluated with using immunofluorescence multi-staining the EMT-associated markers including E-cadherin and alpha-smooth muscle actin (α-SMA), and transcription factors including E-SNAIL and SLUG, and ZEB1. The data were analyzed in specific area, such as tumor center and tumor border. In this study we show that the invasive adenocarcinoma differentially expressed SNAIL and SLUG, and Zeb1 and it was associated with the loss of epithelial marker (E-cadherin) and gaining of mesenchymal marker (α-SMA) at the invasive border of lung carcinoma. The positive rates of SNAIL and ZEB1 were 26.7% and 0% in the tumor center and 40% and 20% in tumor margin, respectively. In addition, the expression of both SNAIL and ZEB1 at the border of tumor was observed in two cases (2/10). These two cases were associated with lymph node metastasis and advanced stage. The process of EMT has been suggested to be of prime importance for tissue and lymphovascular invasion. The process of EMT may be activated in the tumor border of lung adenocarcinoma. Related transcription factors, such as SNAIL and SLUG, and ZEB1, might be induced by paracrine effects of surrounded inflammatory cells and fibroblasts.

Keywords: Epithelial mesenchymal transition; SLUG; SNAIL; ZEB1; lung adenocarcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / analysis
  • Actins / biosynthesis
  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / pathology*
  • Adenocarcinoma of Lung
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis*
  • Cadherins / analysis
  • Cadherins / biosynthesis
  • Epithelial-Mesenchymal Transition / physiology*
  • Female
  • Fluorescent Antibody Technique
  • Homeodomain Proteins / analysis
  • Homeodomain Proteins / biosynthesis
  • Humans
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology*
  • Male
  • Middle Aged
  • Retrospective Studies
  • Snail Family Transcription Factors
  • Transcription Factors / analysis
  • Transcription Factors / biosynthesis
  • Zinc Finger E-box-Binding Homeobox 1

Substances

  • Actins
  • Biomarkers, Tumor
  • Cadherins
  • Homeodomain Proteins
  • SNAI1 protein, human
  • Snail Family Transcription Factors
  • Transcription Factors
  • ZEB1 protein, human
  • Zinc Finger E-box-Binding Homeobox 1