Cancer Metastasis Is Accelerated through Immunosuppression during Snail-Induced EMT of Cancer Cells

Chie Kudo-Saito, Hiromi Shirako, Tadashi Takeuchi, Yutaka Kawakami

Research output: Contribution to journalArticle

477 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)195-206
Number of pages12
JournalCancer Cell
Volume15
Issue number3
DOIs
Publication statusPublished - 2009 Mar 3

Keywords

  • CELLCYCLE
  • CELLIMMUNO

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

Fingerprint Dive into the research topics of 'Cancer Metastasis Is Accelerated through Immunosuppression during Snail-Induced EMT of Cancer Cells'. Together they form a unique fingerprint.

  • Cite this