Open AccessInnate immune sensor laboratory of genetics and physiology 2 suppresses tumor cell growth and functions as a prognostic marker in neuroblastoma
Author(s) -
Lin LiLing,
Huang ChaoCheng,
Wu MinTsui,
Hsu WenMing,
Chuang JiinHaur
Publication year - 2018
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13790
Subject(s) - neuroblastoma , downregulation and upregulation , biology , innate immune system , immune system , ectopic expression , in vitro , cancer research , cytoplasm , gene expression , cell culture , receptor , microbiology and biotechnology , gene , immunology , genetics
The innate immune receptors, such as toll‐like receptor 3 ( TLR 3), melanoma differentiation‐associated 5 ( MDA 5) and retinoic acid‐inducible gene‐I ( RIG ‐I), have been shown to be differentially expressed in neuroblastoma ( NB ) and promote ds RNA poly (I:C)‐induced NB suppression in vitro and in vivo. However, the role of another important innate immune cytosolic sensor, laboratory of genetics and physiology 2 ( LGP 2), in the cancer behavior of NB remains unclear. Here, we demonstrated that the expression levels of LGP 2 were either low or undetectable in all NB cell lines tested with or without MYCN amplification. LGP 2 expression levels were significantly increased only in NB cells without MYCN amplification, including SK ‐N‐ AS and SK ‐N‐ FI after poly (I:C) treatment in vitro and in mouse xenograft models. Ectopic expression of LGP 2 in NB cells significantly enhanced poly (I:C)‐induced NB cell death associated with downregulation of MDA 5, RIG ‐I, MAVS and Bcl‐2, as well as upregulation of Noxa and tB id. By immunofluorescence analyses, LGP 2 localized mainly in the cytoplasm of NB cells after poly (I:C) treatment. In human NB tissue samples, cytoplasmic LGP 2 expression was positively correlated with histological differentiation and inversely correlated with MYCN amplification. Positive cytoplasmic LGP 2 expression in tumor tissues could predict a favorable outcome in NB patients independent of other prognostic factors. In short, LGP 2 was effective in promoting poly (I:C)‐induced NB suppression and cytoplasmic LGP 2 can serve as an independent favorable prognostic factor in NB patients.