Innate immune sensor laboratory of genetics and physiology 2 suppresses tumor cell growth and functions as a prognostic marker in neuroblastoma
Journal
Cancer Science
Journal Volume
109
Journal Issue
11
Pages
3494-3502
Date Issued
2018
Author(s)
Abstract
The innate immune receptors, such as toll-like receptor 3 (TLR3), melanoma differentiation-associated 5 (MDA5) and retinoic acid-inducible gene-I (RIG-I), have been shown to be differentially expressed in neuroblastoma (NB) and promote dsRNA 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 (LGP2), in the cancer behavior of NB remains unclear. Here, we demonstrated that the expression levels of LGP2 were either low or undetectable in all NB cell lines tested with or without MYCN amplification. LGP2 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 LGP2 in NB cells significantly enhanced poly (I:C)-induced NB cell death associated with downregulation of MDA5, RIG-I, MAVS and Bcl-2, as well as upregulation of Noxa and tBid. By immunofluorescence analyses, LGP2 localized mainly in the cytoplasm of NB cells after poly (I:C) treatment. In human NB tissue samples, cytoplasmic LGP2 expression was positively correlated with histological differentiation and inversely correlated with MYCN amplification. Positive cytoplasmic LGP2 expression in tumor tissues could predict a favorable outcome in NB patients independent of other prognostic factors. In short, LGP2 was effective in promoting poly (I:C)-induced NB suppression and cytoplasmic LGP2 can serve as an independent favorable prognostic factor in NB patients. ? 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.
Subjects
LGP2; MDA5; neuroblastoma; polyinosinic-polycytidylic acid; RIG-I
SDGs
Other Subjects
interferon induced helicase C domain containing protein 1; laboratory of genetic and physiology 2 protein; mitochondrial antiviral signaling protein; MYCN protein; protein bcl 2; protein Bid; protein Noxa; retinoic acid inducible protein I; tumor marker; unclassified drug; DHX58 protein, human; polyinosinic polycytidylic acid; RNA helicase; animal experiment; animal model; Article; cancer inhibition; cancer prognosis; child; controlled study; cytoplasm; down regulation; ectopic expression; female; gene amplification; human; human tissue; in vitro study; major clinical study; male; mouse; neuroblastoma; neuroblastoma cell line; nonhuman; priority journal; protein expression; protein localization; tissue differentiation; tumor xenograft; animal; cancer transplantation; cell cycle; cell proliferation; cell survival; down regulation; drug effect; genetics; infant; innate immunity; metabolism; neuroblastoma; preschool child; prognosis; tumor cell line; Animals; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Cell Survival; Child, Preschool; Cytoplasm; Down-Regulation; Female; Humans; Immunity, Innate; Infant; Male; Mice; Neoplasm Transplantation; Neuroblastoma; Poly I-C; Prognosis; RNA Helicases
Publisher
Blackwell Publishing Ltd
Type
journal article