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

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

研究成果: Article査読

549 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)195-206
ページ数12
ジャーナルCancer Cell
15
3
DOI
出版ステータスPublished - 2009 3 3
外部発表はい

ASJC Scopus subject areas

  • 腫瘍学
  • 細胞生物学
  • 癌研究

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