Epithelial-mesenchymal transition regulated by EphA2 contributes to vasculogenic mimicry formation of head and neck squamous cell carcinoma

Biomed Res Int. 2014:2014:803914. doi: 10.1155/2014/803914. Epub 2014 Apr 17.

Abstract

Purpose: Vasculogenic mimicry (VM) was related to invasion and metastasis of head and neck squamous cell carcinoma (HNSCC) patients. This study was designed to investigate the role of EphA2 in VM formation of HNSCC.

Methods: The SiRNA technique was used to knock down the expression of EphA2 in vitro. The ability of cell migration and invasion were measured by transwell and wound healing assays; three-dimensional culture was used to detect the ability of channel-like structure formation; Western blot was used to detect the expression of epithelial-mesenchymal transition- (EMT-) related molecules in vitro. Further semiquantitative real-time RT-PCR assays and immunohistochemistry were used to demonstrate expression of EphA2 and EMT-related molecules according to VM presence or not in human tissue.

Results: Knocking down EphA2 in vitro leads to disabled channel-like structure formation, reduction of invasion and migration ability, and reverse of EMT-related markers. Both semiquantitative real-time RT-PCR and immunohistochemistry showed that expressions of EphA2, Twist, and Vimentin were higher in the VM-positive group than in the VM-negative group significantly, while expressions of E-cadherin, claudin4, and DSG-3 were reverse.

Conclusions: EphA2 played a key role in VM formation of HNSCC through regulation of EMT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Squamous Cell / blood supply*
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / pathology*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Chemotaxis / genetics
  • Down-Regulation / genetics
  • Epithelial-Mesenchymal Transition* / genetics
  • Gene Expression Regulation, Neoplastic
  • Head and Neck Neoplasms / blood supply*
  • Head and Neck Neoplasms / genetics
  • Head and Neck Neoplasms / pathology*
  • Humans
  • Neoplasm Invasiveness
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • Receptor, EphA2 / metabolism*
  • Squamous Cell Carcinoma of Head and Neck
  • Up-Regulation / genetics
  • Wound Healing / genetics

Substances

  • Platelet Endothelial Cell Adhesion Molecule-1
  • Receptor, EphA2