Knockdown of S100A4 impairs arecoline-induced invasiveness of oral squamous cell carcinomas

Oral Oncol. 2015 Jul;51(7):690-7. doi: 10.1016/j.oraloncology.2015.04.003. Epub 2015 Apr 23.

Abstract

Objectives: Metastasis is the most common cause of oral squamous cell carcinoma (OSCC)-related death. The physiological function of S100A4 in the pathogenesis of areca quid chewing-associated OSCC has not been uncovered.

Method: OSCC tissues from areca quid chewers were analyzed by immunohistochemistry for S100A4 expression. The functions of S100A4 in invasiveness of arecoline-treated oral epithelial (OE) cells were determined by loss function approaches.

Results: Expression of S100A4 was positively correlated with clinical grading and lymph node metastasis of OSCC. Upregulated S100A4 is correlated with poor survival outcome of OSCC patients. Arecoline led to dose-dependent elevation of S100A4 expression in oral epithelial (OE) cells. Down-regulation of S100A4 significantly reversed arecoline-induced oncogenecity in OE cells. The additions of pharmacological agents LY294002, SP600125, and CAY10585 were found to inhibit arecoline-induced S100A4 expression in OE cells.

Conclusion: Arecoline-induced S100A4 expression was down-regulated by LY294002, SP600125, or CAY10585 treatment. Targeting S100A4 might offer a new strategy for the treatment of OSCC patients with metastasis.

Keywords: Arecoline; Invasiveness; Oncogenecity; Oral squamous cell carcinomas; S100A4.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anthracenes / pharmacology
  • Areca / adverse effects
  • Carcinoma, Squamous Cell / chemically induced
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / pathology*
  • Chromones / pharmacology
  • Enzyme Inhibitors / pharmacology
  • Female
  • Humans
  • Lymphatic Metastasis
  • Male
  • Mastication
  • Morpholines / pharmacology
  • Mouth Mucosa / drug effects
  • Mouth Mucosa / metabolism
  • Mouth Mucosa / pathology*
  • Mouth Neoplasms / chemically induced
  • Mouth Neoplasms / mortality
  • Mouth Neoplasms / pathology*
  • Neoplasm Invasiveness
  • S100 Calcium-Binding Protein A4
  • S100 Proteins / drug effects
  • S100 Proteins / metabolism*
  • Survival Rate

Substances

  • Anthracenes
  • Chromones
  • Enzyme Inhibitors
  • Morpholines
  • S100 Calcium-Binding Protein A4
  • S100 Proteins
  • S100A4 protein, human
  • pyrazolanthrone
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one