RRC ID 52690
Author Taki M, Abiko K, Baba T, Hamanishi J, Yamaguchi K, Murakami R, Yamanoi K, Horikawa N, Hosoe Y, Nakamura E, Sugiyama A, Mandai M, Konishi I, Matsumura N.
Title Snail promotes ovarian cancer progression by recruiting myeloid-derived suppressor cells via CXCR2 ligand upregulation.
Journal Nat Commun
Abstract Snail is a major transcriptional factor that induces epithelial-mesenchymal transition (EMT). In this study, we explore the effect of Snail on tumor immunity. Snail knockdown in mouse ovarian cancer cells suppresses tumor growth in immunocompetent mice, associated with an increase of CD8+ tumor-infiltrating lymphocytes and a decrease of myeloid-derived suppressor cells (MDSCs). Snail knockdown reduces the expression of CXCR2 ligands (CXCL1 and CXCL2), chemokines that attract MDSCs to the tumor via CXCR2. Snail upregulates CXCR ligands through NF-kB pathway, and most likely, through direct binding to the promoters. A CXCR2 antagonist suppresses MDSC infiltration and delays tumor growth in Snail-expressing mouse tumors. Ovarian cancer patients show elevated serum CXCL1/2, which correlates with Snail expression, MDSC infiltration, and short overall survival. Thus, Snail induces cancer progression via upregulation of CXCR2 ligands and recruitment of MDSCs. Blocking CXCR2 represents an immunological therapeutic approach to inhibit progression of Snail-high tumors undergoing EMT.
Volume 9(1)
Pages 1685
Published 2018-4-27
DOI 10.1038/s41467-018-03966-7
PII 10.1038/s41467-018-03966-7
PMID 29703902
PMC PMC5923228
MeSH Animals Chemokine CXCL1 / blood Chemokine CXCL1 / metabolism Chemokine CXCL2 / blood Chemokine CXCL2 / metabolism Disease Progression Epithelial-Mesenchymal Transition / genetics Epithelial-Mesenchymal Transition / immunology Female Gene Expression Regulation, Neoplastic / immunology Gene Knockdown Techniques Humans Mice Mice, Inbred ICR Mice, Nude Middle Aged Myeloid-Derived Suppressor Cells / immunology* Ovarian Neoplasms / blood Ovarian Neoplasms / genetics Ovarian Neoplasms / immunology* Ovarian Neoplasms / mortality Receptors, Interleukin-8B / antagonists & inhibitors Receptors, Interleukin-8B / immunology* Receptors, Interleukin-8B / metabolism Signal Transduction Snail Family Transcription Factors / genetics Snail Family Transcription Factors / metabolism* Up-Regulation Xenograft Model Antitumor Assays
IF 12.121
Times Cited 49
Human and Animal Cells OV2944-HM-1(RCB1483) JHOS-2(RCB1521)