Versican G3 promotes mouse mammary tumor cell growth, migration, and metastasis by influencing EGF receptor signaling.
Versican G3 promotes mouse mammary tumor cell growth, migration, and metastasis by influencing EGF receptor signaling.
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DOI：
10.1371/journal.pone.0013828
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发表时间：
2010-11-05
期刊：
影响因子：
3.7
通讯作者：
Yee AJ
中科院分区：
文献类型：
--
作者：
Du WW;Yang BB;Shatseva TA;Yang BL;Deng Z;Shan SW;Lee DY;Seth A;Yee AJ
乳腺肿瘤中versican表达的增加预示着复发，并对生存率有负面影响。在临床前小鼠模型中，versican的c端G3结构域影响局部和全身肿瘤的侵袭性。然而，G3影响乳腺肿瘤生长和转移的机制尚不清楚。我们在小鼠乳腺肿瘤细胞系中检测了versican的表达，发现4T1细胞表达量最高，而66c14细胞表达量较低。我们在66c14细胞中外源表达了G3构建体，并分析了其对细胞增殖、迁移、细胞周期进展和EGFR信号传导的影响。同基因原位动物模型实验表明，G3在体内促进肿瘤生长和全身转移。pERK的激活与高水平的G3表达相关。在体外，G3通过上调EGFR信号通路促进乳腺癌细胞的增殖和迁移，并通过趋化机制增强骨基质细胞的移动性，而这种作用被抑制剂AG 1478阻止。表达G3的细胞CDK2和GSK-3β (S9P)表达增加，这与细胞生长有关。上调egfr介导的信号通路可调节G3对小鼠乳腺肿瘤细胞生长、迁移及骨转移的影响。综上所述，egfr信号似乎是versican g3介导的乳腺癌肿瘤侵袭和转移的重要途径。
Increased versican expression in breast tumors is predictive of relapse and has negative impact on survival rates. The C-terminal G3 domain of versican influences local and systemic tumor invasiveness in pre-clinical murine models. However, the mechanism(s) by which G3 influences breast tumor growth and metastasis is not well characterized. Here we evaluated the expression of versican in mouse mammary tumor cell lines observing that 4T1 cells expressed highest levels while 66c14 cells expressed low levels. We exogenously expressed a G3 construct in 66c14 cells and analyzed its effects on cell proliferation, migration, cell cycle progression, and EGFR signaling. Experiments in a syngeneic orthotopic animal model demonstrated that G3 promoted tumor growth and systemic metastasis in vivo. Activation of pERK correlated with high levels of G3 expression. In vitro, G3 enhanced breast cancer cell proliferation and migration by up-regulating EGFR signaling, and enhanced cell motility through chemotactic mechanisms to bone stromal cells, which was prevented by inhibitor AG 1478. G3 expressing cells demonstrated increased CDK2 and GSK-3β (S9P) expression, which were related to cell growth. The activity of G3 on mouse mammary tumor cell growth, migration and its effect on spontaneous metastasis to bone in an orthotopic model was modulated by up-regulating the EGFR-mediated signaling pathway. Taken together, EGFR-signaling appears to be an important pathway in versican G3-mediated breast cancer tumor invasiveness and metastasis.
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影响因子：
3.7
作者：
Kong A;Calleja V;Leboucher P;Harris A;Parker PJ;Larijani B
通讯作者：
Larijani B
影响因子：
4.8
作者：
Chen, G;Hitomi, M;Stacey, DW
通讯作者：
Stacey, DW
影响因子：
4.8
作者：
Kawashima, H;Hirose, M;Miyasaka, M
通讯作者：
Miyasaka, M
DOI：
10.1073/pnas.92.23.10590
发表时间：
1995-11-07
影响因子：
11.1
作者：
ASPBERG, A;BINKERT, C;RUOSLAHTI, E
通讯作者：
RUOSLAHTI, E
影响因子：
4.7
作者：
Cross, DAE;Culbert, AA;Reith, AD
通讯作者：
Reith, AD