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2018 ; 8
(1
): 5717
Nephropedia Template TP
gab.com Text
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English Wikipedia
Plac1 Is a Key Regulator of the Inflammatory Response and Immune Tolerance In
Mammary Tumorigenesis
#MMPMID29632317
Yuan H
; Wang X
; Shi C
; Jin L
; Hu J
; Zhang A
; Li J
; Vijayendra N
; Doodala V
; Weiss S
; Tang Y
; Weiner LM
; Glazer RI
Sci Rep
2018[Apr]; 8
(1
): 5717
PMID29632317
show ga
Plac1 is an X-linked trophoblast gene expressed at high levels in the placenta,
but not in adult somatic tissues other than the testis. Plac1 however is
re-expressed in several solid tumors and in most human cancer cell lines. To
explore the role of Plac1 in cancer progression, Plac1 was reduced by RNA
interference in EO771 mammary carcinoma cells. EO771 "knockdown" (KD) resulted in
50% reduction in proliferation in vitro and impaired tumor growth in syngeneic
mice; however, tumor growth in SCID mice was equivalent to tumor cells expressing
a non-silencing control RNA, suggesting that Plac1 regulated adaptive immunity.
Gene expression profiling of Plac1 KD cells indicated reduction in several
inflammatory and immune factors, including Cxcl1, Ccl5, Ly6a/Sca-1, Ly6c and Lif.
Treatment of mice engrafted with wild-type EO771 cells with a Cxcr2 antagonist
impaired tumor growth, reduced myeloid-derived suppressor cells and regulatory T
cells, while increasing macrophages, dendritic cells, NK cells and the
penetration of CD8+ T cells into the tumor bed. Cxcl1 KD phenocopied the effects
of Plac1 KD on tumor growth, and overexpression of Cxcl1 partially rescued Plac1
KD cells. These results reveal that Plac1 modulates a tolerogenic tumor
microenvironment in part by modulating the chemokine axis.