Leucine-rich α-2-glycoprotein promotes TGFβ1-mediated growth suppression in the Lewis lung carcinoma cell lines.
Leucine-rich α-2-glycoprotein promotes TGFβ1-mediated growth suppression in the Lewis lung carcinoma cell lines.
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DOI：
10.18632/oncotarget.3557
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发表时间：
2015-05-10
期刊：
影响因子：
--
通讯作者：
Naka T
中科院分区：
文献类型：
--
作者：
Takemoto N;Serada S;Fujimoto M;Honda H;Ohkawara T;Takahashi T;Nomura S;Inohara H;Naka T
富含亮氨酸的α2-糖蛋白（LRG）是一种约50 kDa的糖蛋白，已发现其在几种类型癌症患者的血清中升高。LRG直接与转化生长因子β 1（TGFβ1）结合并调节内皮细胞中的TGFβ1信号传导;然而，LRG在癌症中的确切功能仍不清楚。本研究旨在探讨LRG在癌症中的作用。刘易斯肺癌（LLC）细胞几乎不表达LRG。与野生型（WT）小鼠相比，在LRG敲除（KO）小鼠中同种异体移植的LLC肿瘤的生长显著增加。相反，LRG的过表达显著抑制WT小鼠中LLC肿瘤的生长。在LRG存在下，TGFβ1通过激活smad 2及其下游信号通路诱导细胞凋亡，从而显著抑制LLC细胞和人肝癌Hep 3B细胞的增殖。此外，与LRG KO小鼠相比，TGFβR1抑制剂（SB 431542）给药通过抑制细胞凋亡显著增强了WT小鼠LLC肿瘤的生长。我们认为，LRG增强了TGFβ1在癌细胞中的作用，这些癌细胞的生长在TGFβ1的存在下受到抑制。
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.
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DOI：
10.1515/bchm2.1977.358.1.639
发表时间：
1977-01-01
影响因子：
--
作者：
HAUPT, H;BAUDNER, S
通讯作者：
BAUDNER, S
影响因子：
7
作者：
Finnson, K. W.;Parker, W. L.;Philip, A.
通讯作者：
Philip, A.
ID样分子HHM是TGF-β信号传导的Synexpression群体限制调节剂。
影响因子：
11.4
作者：
Ikushima, Hiroaki;Komuro, Akiyoshi;Isogaya, Kazunobu;Shinozaki, Masahiko;Hellman, Ulf;Miyazawa, Keiji;Miyazono, Kohei
通讯作者：
Miyazono, Kohei
TGFβ 信号的背景
DOI：
10.1038/nrm3434
发表时间：
2012-10
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1073/pnas.91.19.8772
发表时间：
1994-09-13
影响因子：
11.1
作者：
PARK, KC;KIM, SJ;SPORN, MB
通讯作者：
SPORN, MB