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

436 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

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Epithelial-Mesenchymal Transition
Immunosuppression
Neoplasm Metastasis
Neoplasms
Snails
Melanoma
Tumor-Infiltrating Lymphocytes
Immunotherapy
Dendritic Cells
Small Interfering RNA
Transcription Factors
Monoclonal Antibodies
Injections
Growth

Keywords

  • CELLCYCLE
  • CELLIMMUNO

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Oncology

Cite this

Cancer Metastasis Is Accelerated through Immunosuppression during Snail-Induced EMT of Cancer Cells. / Kudo-Saito, Chie; Shirako, Hiromi; Takeuchi, Tadashi; Kawakami, Yutaka.

In: Cancer Cell, Vol. 15, No. 3, 03.03.2009, p. 195-206.

Research output: Contribution to journalArticle

Kudo-Saito, Chie ; Shirako, Hiromi ; Takeuchi, Tadashi ; Kawakami, Yutaka. / Cancer Metastasis Is Accelerated through Immunosuppression during Snail-Induced EMT of Cancer Cells. In: Cancer Cell. 2009 ; Vol. 15, No. 3. pp. 195-206.
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