Leucine-rich ?-2-glycoprotein promotes TGF?1-mediated growth suppression in the Lewis lung carcinoma cell lines.

ABSTRACT: Leucine-rich ?2-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 (TGF?1) and modulates TGF?1 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, TGF?1 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 TGF?R1 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 TGF?1 in cancer cells whose growth is suppressed in the presence of TGF?1.

SUBMITTER: Takemoto N 

PROVIDER: S-EPMC4484435 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature