Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=29703902
&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215
Snail promotes ovarian cancer progression by recruiting myeloid-derived
suppressor cells via CXCR2 ligand upregulation
#MMPMID29703902
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
Nat Commun
2018[Apr]; 9
(1
): 1685
PMID29703902
show ga
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.
free
free
free
