The Lectin-Like Domain of Thrombomodulin Inhibits β1 Integrin-Dependent Binding of Human Breast Cancer-Derived Cell Lines to Fibronectin.
The Lectin-Like Domain of Thrombomodulin Inhibits β1 Integrin-Dependent Binding of Human Breast Cancer-Derived Cell Lines to Fibronectin.
复制标题
DOI：
10.3390/biomedicines9020162
复制
发表时间：
2021-02-07
期刊：
影响因子：
4.7
通讯作者：
Shimaoka M
中科院分区：
文献类型：
--
作者：
Kawamoto E;Nago N;Okamoto T;Gaowa A;Masui-Ito A;Akama Y;Darkwah S;Appiah MG;Myint PK;Obeng G;Ito A;Caidengbate S;Esumi R;Yamaguchi T;Park EJ;Imai H;Shimaoka M
凝血调节素是一种具有抗凝和抗炎特性的分子。最近，据报道血栓调节蛋白能够结合细胞外基质蛋白，如纤维连接蛋白和胶原蛋白；然而，凝血调节蛋白是否调节人乳腺癌来源细胞系与细胞外基质的结合尚不清楚。为了研究这一点，我们创建了血栓调节蛋白的细胞外结构域TMD123-Fc或结构域缺失的TM- fc蛋白（TM结构域12-Fc， TM结构域23-Fc），并通过ELISA检测了它们与纤维连接蛋白的结合。凝血调节蛋白的凝集素样结构域被发现对于凝血调节蛋白的细胞外结构域与纤连蛋白的结合至关重要。通过v孔细胞粘附实验或荧光珠流式细胞术分析，我们发现TMD123-Fc和TMD12-Fc均抑制人乳腺癌源性细胞系β1整合素与纤维连接蛋白的结合。此外，TMD123-Fc和TMD12-Fc在Ca2+和Mg2+存在的剪切应力下抑制活化的整合素与纤维连接蛋白的结合，而在Mg2+不含Ca2+存在的强整合素激活条件下则没有。这表明，在炎症的相对早期阶段外源性给予血栓调节蛋白Fc融合蛋白可能用于开发抑制乳腺癌细胞系β1整合素与纤维连接蛋白结合的新疗法。
Thrombomodulin is a molecule with anti-coagulant and anti-inflammatory properties. Recently, thrombomodulin was reported to be able to bind extracellular matrix proteins, such as fibronectin and collagen; however, whether thrombomodulin regulates the binding of human breast cancer-derived cell lines to the extracellular matrix remains unknown. To investigate this, we created an extracellular domain of thrombomodulin, TMD123-Fc, or domain deletion TM-Fc proteins (TM domain 12-Fc, TM domain 23-Fc) and examined their bindings to fibronectin in vitro by ELISA. The lectin-like domain of thrombomodulin was found to be essential for the binding of the extracellular domain of thrombomodulin to fibronectin. Using a V-well cell adhesion assay or flow cytometry analysis with fluorescent beads, we found that both TMD123-Fc and TMD12-Fc inhibited the binding between β1 integrin of human breast cancer-derived cell lines and fibronectin. Furthermore, TMD123-Fc and TMD12-Fc inhibited the binding of activated integrins to fibronectin under shear stress in the presence of Ca2+ and Mg2+ but not under strong integrin-activation conditions in the presence of Mg2+ without Ca2+. This suggests that thrombomodulin Fc fusion protein administered exogenously at a relatively early stage of inflammation may be applied to the development of new therapies that inhibit the binding of β1 integrin of breast cancer cell lines to fibronectin.
登录
查看更多内容
影响因子：
2.4
作者：
BANERJEE, AK;ANGULO, AF;KERSHOF, AM
通讯作者：
KERSHOF, AM
影响因子：
7.5
作者：
Iba, Toshiaki;Aihara, Koichiro;Yang, Daphne
通讯作者：
Yang, Daphne
影响因子：
4
作者：
Humphries JD;Byron A;Humphries MJ
通讯作者：
Humphries MJ
DOI：
10.1046/j.1432-1327.1999.00398.x
发表时间：
1999-06-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
Light, DR;Glaser, CB;Morser, J
通讯作者：
Morser, J
影响因子：
37.3
作者：
Dingemans AM;van den Boogaart V;Vosse BA;van Suylen RJ;Griffioen AW;Thijssen VL
通讯作者：
Thijssen VL