Journal
CANCER CELL
Volume 15, Issue 3, Pages 195-206Publisher
CELL PRESS
DOI: 10.1016/j.ccr.2009.01.023
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Funding
- Japanese Ministry of Education, Culture, Sports, Science and Technology [18591484, 19390355, 17016070]
- Uehara Memorial Foundation
- Yasuda Medical Foundation
- Grants-in-Aid for Scientific Research [18591484, 17016070, 19390355] Funding Source: KAKEN
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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.
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