Epithelial-mesenchymal transition and mesenchymal-epithelial transition via regulation of ZEB-1 and ZEB-2 expression in pancreatic cancer

J Surg Oncol. 2012 Jun 1;105(7):655-61. doi: 10.1002/jso.23020. Epub 2011 Dec 27.

Abstract

BACKGROUND AND OBJECTIES: Phenotypic plasticity of cancer cells via epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) is essential for tumor progression and metastasis.

Methods: Tissue samples were obtained from 76 pancreatic head cancers. We assessed the expression of E-cadherin, vimentin, ZEB-1, and ZEB-2 by immunohistochemical and immunofluorescence staining. Next, 147 metastatic lymph nodes from 45 pancreatic cancers with low expression of E-cadherin were obtained and divided into two categories according to the maximum diameter of the metastases: 2 mm or more and less than 2 mm.

Results: High expressions of ZEB-1 and ZEB-2 in the primary tumors were significantly associated with repression of E-cadherin (P = 0.0007), and poorer prognosis (P = 0.0322). Forty-three (29.3%) of the 147 metastatic tumors from pancreatic cancers with low expression of E-cadherin showed high E-cadherin expression. Cancer cells in the larger metastases showed high expression of E-cadherin (P = 0.0061) and low expression of ZEB-1 (P = 0.0170) and ZEB-2 (P = 0.0036) compared with those in the smaller metastases.

Conclusions: In primary pancreatic tumors and metastatic lymph nodes, high and low expression of ZEB-1 and ZEB-2 was associated with mesenchymal and epithelial phenotype of cancer cells, respectively.

MeSH terms

  • Aged
  • Cadherins / analysis
  • Epithelial-Mesenchymal Transition*
  • Female
  • Homeodomain Proteins / analysis*
  • Homeodomain Proteins / physiology
  • Humans
  • Immunohistochemistry
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Pancreatic Neoplasms / chemistry
  • Pancreatic Neoplasms / pathology*
  • Repressor Proteins / analysis*
  • Repressor Proteins / physiology
  • Transcription Factors / analysis*
  • Transcription Factors / physiology
  • Vimentin / analysis
  • Zinc Finger E-box Binding Homeobox 2
  • Zinc Finger E-box-Binding Homeobox 1

Substances

  • Cadherins
  • Homeodomain Proteins
  • Repressor Proteins
  • Transcription Factors
  • Vimentin
  • ZEB1 protein, human
  • ZEB2 protein, human
  • Zinc Finger E-box Binding Homeobox 2
  • Zinc Finger E-box-Binding Homeobox 1