Antisense-Snail transfer inhibits tumor metastasis by inducing E-cadherin expression

Anticancer Res. 2008 Mar-Apr;28(2A):621-8.

Abstract

Carcinoma cell metastasis is mediated by increased mobility and invasiveness via epithelial-mesenchymal transition (EMT). Snail, a zinc-finger transcription factor, triggers EMT by directly repressing E-cadherin expression. In this study, the correlation between E-cadherin and Snail expression was investigated. In addition, the effect of antisense-Snail on the mobility and invasive properties of tumor cells in vitro and in vivo was assessed. Our data showed that Snail induced EMT, up-regulated mesenchymal gene expression and increased the ability of cancer cells to migrate and invade. In contrast, antisense-Snail prevented EMT by decreasing the expression of mesenchymal genes, and inhibited the migration and invasive potential in vitro. An in situ xenograft model showed that adenovirus-mediated antisense-Snail expression inhibited tumor cell metastasis to the lymph nodes and prolonged the survival of the hosts. These findings suggest that Snail plays a critical role in EMT and subsequent invasiveness. Snail inhibition may serve as a promising target for therapeutic strategies to prevent tumor metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cadherins / metabolism*
  • Cell Line
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Lymphatic Metastasis / prevention & control*
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Invasiveness / prevention & control*
  • Snail Family Transcription Factors
  • Transcription Factors / physiology*
  • Transfection
  • Xenograft Model Antitumor Assays

Substances

  • Cadherins
  • Snail Family Transcription Factors
  • Transcription Factors