title: Leucine-rich α-2-glycoprotein promotes TGFβ1-mediated growth suppression in the Lewis lung carcinoma cell lines.
abstract: Leucine-rich α2-glycoprotein (LRG) is an approximately 50-kDa glycoprotein that has been found to be elevated in the sera of patients with several types of cancer. LRG directly binds to transforming growth factor beta 1 (TGFβ1) and modulates TGFβ1 signaling in endothelial cells; however, the precise function of LRG in cancer remains unclear. This study aimed to investigate the role of LRG in cancer. Lewis lung carcinoma (LLC) cells hardly expressed LRG. The growth of LLC tumors allografted in the LRG knockout (KO) mice was significantly increased compared with wild-type (WT) mice. Conversely, overexpression of LRG significantly inhibited the growth of LLC tumors in WT mice. In the presence of LRG, TGFβ1 significantly inhibited the proliferation of LLC cells and human hepatocellular carcinoma Hep3B cells in vitro by inducing apoptosis via the potent activation of smad2 and its downstream signaling pathway. Furthermore, administration of a TGFβR1 inhibitor (SB431542) significantly enhanced the growth of LLC tumors in WT mice compared with LRG KO mice via inhibition of apoptosis. We propose that LRG potentiates the effect of TGFβ1 in cancer cells whose growth is suppressed in the presence of TGFβ1.
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Osaka University Graduate School of Medicine, Ibaraki, Osaka, Japan.|Laboratory of Immune Signal, National Institute of Biomedical Innovation, Ibaraki, Osaka, Japan.
authors.forename: Norihiko
authors.initials: N
authors.lastname: Takemoto
authors.affiliation: Laboratory of Immune Signal, National Institute of Biomedical Innovation, Ibaraki, Osaka, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Serada
authors.affiliation: Laboratory of Immune Signal, National Institute of Biomedical Innovation, Ibaraki, Osaka, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Fujimoto
authors.affiliation: Laboratory of Immune Signal, National Institute of Biomedical Innovation, Ibaraki, Osaka, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Honda
authors.affiliation: Laboratory of Immune Signal, National Institute of Biomedical Innovation, Ibaraki, Osaka, Japan.
authors.forename: Tomoharu
authors.initials: T
authors.lastname: Ohkawara
authors.affiliation: Laboratory of Immune Signal, National Institute of Biomedical Innovation, Ibaraki, Osaka, Japan.|Department of Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Takahashi
authors.affiliation: Department of Animal Bioscience, Nagahama Institute of Bio-Science and Technology, Ibaraki, Osaka, Japan.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Nomura
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Osaka University Graduate School of Medicine, Ibaraki, Osaka, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Inohara
authors.affiliation: Laboratory of Immune Signal, National Institute of Biomedical Innovation, Ibaraki, Osaka, Japan.
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Naka
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D018827:Carcinoma, Lewis Lung / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D049109:Cell Proliferation; D005260:Female; D006023:Glycoproteins / Q000502:physiology*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D006023:Glycoproteins; C530631:LRG1 protein, mouse; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1
keywords: Lewis lung carcinoma; TGFβ; apoptosis; leucine-rich α-2-glycoprotein; smad signal transduction
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