Cancer metastasis is accelerated through immunosuppression during Snail-induced EMT of cancer cells

Cancer Cell. 2009 Mar 3;15(3):195-206. doi: 10.1016/j.ccr.2009.01.023.

Abstract

Epithelial-mesenchymal transition (EMT) is a key step toward cancer metastasis, and Snail is a major transcription factor governing EMT. Here, we demonstrate that Snail-induced EMT accelerates cancer metastasis through not only enhanced invasion but also induction of immunosuppression. Murine and human melanoma cells with typical EMT features after snail transduction induced regulatory T cells and impaired dendritic cells in vitro and in vivo partly through TSP1 production. Although Snail(+) melanoma did not respond to immunotherapy, intratumoral injection with snail-specific siRNA or anti-TSP1 monoclonal antibody significantly inhibited tumor growth and metastasis following increase of tumor-specific tumor-infiltrating lymphocytes and systemic immune responses. These results suggest that inhibition of Snail-induced EMT could simultaneously suppress both tumor metastasis and immunosuppression in cancer patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Transformation, Neoplastic / immunology*
  • Dendritic Cells / immunology
  • Flow Cytometry
  • Humans
  • Immune Tolerance*
  • Immunohistochemistry
  • Immunotherapy
  • Melanoma, Experimental / immunology*
  • Melanoma, Experimental / pathology*
  • Neoplasm Invasiveness / immunology*
  • RNA, Small Interfering
  • Reverse Transcriptase Polymerase Chain Reaction
  • Snail Family Transcription Factors
  • T-Lymphocytes, Regulatory / immunology
  • Transcription Factors / genetics
  • Transcription Factors / immunology*
  • Transcription Factors / metabolism
  • Transduction, Genetic
  • Transfection

Substances

  • RNA, Small Interfering
  • Snail Family Transcription Factors
  • Transcription Factors